Analogues of polyamine alkaloids and their synthetic advantages

Several polyamine derivatives were synthesized in order to produce novel antagonists of muscular nicotinic acetylcholine receptors. Their affinities were compared with those of philanthotoxin PhTX-343.

Characterization of choline uptake in Trypanosoma brucei procyclic and bloodstream forms

Choline is an essential nutrient for eukaryotic cells, where it is used as precursor for the synthesis of choline-containing phospholipids, such as phosphatidylcholine (PC). According to published data, Trypanosoma brucei parasites are unable to take up choline from the environment but instead use lyso-phosphatidylcholine as precursor for choline lipid synthesis. We now show that T. brucei procyclic forms in culture readily incorporate [3H]-labeled choline into PC, indicating that trypanosomes express a transporter for choline at the plasma membrane. Characterization of the transport system in T. brucei procyclic and bloodstream forms shows that uptake of choline is independent of sodium and potassium ions and occurs with a Km in the low micromolar range. In addition, we demonstrate that choline uptake can be blocked by the known choline transport inhibitor, hemicholinium-3, and by synthetic choline analogs that have been established as anti-malarials. Together, our results show that T. brucei parasites express an uptake system for choline and that exogenous choline is used for PC synthesis.

Facile Synthesis of Novel Functionalized Bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) Derivatives

An improved and efficient synthetic route to four functionalized bis(ethylenedithio)-tetrathiafulvalene (BEDT-TTF) derivatives 2−5 is reported. Tetrathiolate 1 was readily prepared from 2,2‘-bis(1,3,4,6-tetrathiapentalen-5-one) under carefully controlled conditions. Subsequent reaction of 1 with selected primary alkyl halides affords new functionalized BEDT-TTF derivatives in good yields.

Glacial–interglacial temperature change in the tropical West Pacific: A comparison of stalagmite-based paleo-thermometers

In the tropics, geochemical records from stalagmites have so far mainly been used to qualitatively reconstruct changes in precipitation, but several new methods to reconstruct past temperatures from stalagmite material have emerged recently: i) liquide vapor homogenization of fluid inclusion water ii) noble gas concentrations in fluid inclusion water, iii) the partitioning of oxygen isotopes between fluid inclusion water and calcite, and iv) the abundance of the 13C18O16O(‘clumped’) isotopologue in calcite. We present, for the first time, a direct comparison of these four paleo-thermometers by applying them to a fossil stalagmite covering nearly two glaciale interglacial cycles (Marine Isotope Stages (MIS) 12 e 9) and to two modern stalagmites, all from northern Borneo. The temperature estimates from the different methods agree in most cases within errors for both the old and recent samples; reconstructed formation temperatures of the recent samples match within 2-sigma errors with measured cave temperatures. However, slight but systematic deviations are observed between noble gas and liquide vapor homogenization temperatures. Whereas the temperature sensitivity of fluid inclusion d18O and clumped isotopes is currently debated, we find that the calibration of Tremaine et al. (2011) for fluid inclusion d18O and a synthetic calcite-based clumped isotope calibration (Ziegler et al., in prep.) yield temperature estimates consistent with the other methods. All methods (with the potential exception of clumped isotopes) show excellent agreement on the amplitude of glaciale interglacial temperature change, indicating temperature shifts of 4-5 C°. This amplitude is similar to the amplitude of Mg/Ca-based regional sea surface temperature records, when correcting for sea level driven changes in cave elevation. Our reconstruction of tropical temperature evolution over the time period from 440 to 320 thousand years ago (ka) adds support to the view that climate sensitivity to varying greenhouse forcing is substantial also in the deep tropics.

Liquid-Crystalline Dendrimers Designed by Click Chemistry

Liquid-crystalline dendrimers have been prepared from second-generation Percec-type poly(benzyl ether) dendrons or second-generation poly(aryl ester) dendrons carrying cyanobiphenyl mesogens. The Janus dendrimer, which combines the two types of dendromesogens, has also been synthesized. Those compounds have been prepared under copper-catalyzed azide–alkyne cycloaddition conditions. The mesomorphic properties have been studied by thermal analysis (POM, DSC) and small-angle X-ray scattering. Smectic A, nematic, and columnar phases have been observed depending on the dendritic building blocks. The click reaction has proven to be a powerful and elegant synthetic tool for the design of complex dendritic liquid-crystalline architectures.

Synthetic-echo time postprocessing technique for generating images with variable T2-weighted contrast: diagnosis of meniscal and cartilage abnormalities of the knee

To assess the feasibility and accuracy of a synthetic-echo time (TE) magnetic resonance (MR) postprocessing technique for the diagnostic evaluation of abnormalities of menisci and articular cartilage in the knee.

Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantitation of synthetic cannabinoids of the aminoalkylindole type and methanandamide in serum and its application to forensic samples

After the discovery of synthetic cannabimimetic substances in 'Spice'-like herbal mixtures marketed as 'incense' or 'plant fertilizer' the active compounds have been declared as controlled substances in several European countries. As expected, a monitoring of new herbal mixtures which continue to appear on the market revealed that shortly after control measures have been taken by legal authorities, other compounds were added to existing mixtures and to new products. Several compounds of the aminoalkylindole type have been detected so far in herbal mixtures but still their consumption cannot be detected by commonly used drug-screening procedures, encouraging drug users to substitute cannabis with those products. There is a increasing demand on the part of police authorities, hospitals and psychiatrists for detection and quantification of synthetic cannabinoids in biological samples originating from psychiatric inpatients, emergency units or assessment of fitness to drive. Therefore, a liquid chromatography-tandem mass spectrometry method after liquid-liquid extraction for the quantitation of JWH-015, JWH-018, JWH-073, JWH-081, JWH 200, JWH-250, WIN 55,212-2 and methanandamide and the detection of JWH-019 and JWH-020 in human serum has been developed and fully validated according to guidelines for forensic toxicological analyses. The method was successfully applied to 101 serum samples from 80 subjects provided by hospitals, detoxification and therapy centers, forensic psychiatric centers and police authorities. Fifty-seven samples or 56.4% were found positive for at least one aminoalkylindole. JWH-019, JWH-020, JWH-200, WIN 55,212-2 and methanandamide were not detected in any of the analyzed samples.

Design and construction of a new Drosophila species, D.synthetica, by synthetic regulatory evolution

Here, I merge the principles of synthetic biology1,2 and regulatory evolution3-11 to create a new species12-15 with a minimal set of known elements. Using preexisting transgenes and recessive mutations of Drosophila melanogaster, a transgenic population arises with small eyes and a different venation pattern that fulfills the criteria of a new species according to Mayr's "Biological Species Concept"7,10. The genetic circuit entails the loss of a non-essential transcription factor and the introduction of cryptic enhancers. Subsequent activation of those enhancers causes hybrid lethality. The transition from "transgenic organisms" towards "synthetic species", such as Drosophila synthetica, constitutes a safety mechanism to avoid hybridization with wild type populations and preserve natural biodiversity16-18. Drosophila synthetica is the first transgenic organism that cannot hybridize with the original wild type population but remains fertile when crossed with other transgenic animals.

Effects of dietary supplementation with synthetic vitamin D-3 and 25-hydroxycholecalciferol on blood calcium and phosphate levels and performance in laying hens

We investigated the effects of different dietary vitamin D regimen on selected blood parameters in laying hens. Supplementation with vitamin D-3 only was compared with a combination of vitamin D-3 and its metabolite 25-hydroxy-cholecalciferol (25(OH)D-3). Blood concentrations of total calcium, phosphate and 25 (OH)D-3 were determined. Four thousand one-day-old LSL chicks were split in two treatment groups and distributed to eight pens. The control group was given a commercial animal diet containing 2800 IU synthetic vitamin D-3 in the starter feed and 2000 IU synthetic vitamin D-3 in the pullet feed. The experimental group was fed the same commercial diet in which half the synthetic vitamin D-3 content had been substituted with 25(OH)D-3 (Hy center dot D (R)). At 18 weeks of age, pullets were transferred to the layer house. At the ages of 11, 18 and 34 weeks, between 120 and 160 blood samples were collected from both the control and the experimental groups, respectively. The experimental group had higher levels of 25 (OH)D-3 than the control group at all three ages. Serum calcium levels did not differ between the treatment groups at any age. With the onset of laying, calcium levels rose significantly. Whereas blood serum concentration at 18 weeks was 3 mmol/L in both treatment groups, it increased to 8.32 mmol/L in the control group and to 8.66 mmol/L in the experimental group at week 34. At weeks 11 and 34, phosphate was significantly lower in the experimental group. In conclusion, HyD (R) significantly affected serum phosphate and 25(OH)D-3 levels. No effects of (25(OH)D-3 supplementation on performance, shell quality and fractures of keelbones were found.