Abstract:In order to use speleothems in the reconstruction of past climate and environmental changes it is necessary to understand the environmental and hydrological processes that determine the physico-chemical conditions of carbonate precipitation and hence speleothem formation. Therefore, in this study an extended monitoring program was conducted in the Béke and Baradla caves located in the Aggtelek region (Northeastern Hungary). The studied caves are rich in speleothem and flowstone occurrences with great potential for paleoclimatology studies. The monitoring activity included measurements of atmospheric and cave temperatures, CO 2 concentration in cave air, as well as chemical and isotopic compositions of water samples (drip water, precipitation) and in situ carbonate precipitates. The hydrogen and oxygen isotope compositions of drip waters showed no seasonal variation at any of the collection sites, indicating a well-mixed karstic aquifer. This implies that the isotopic compositions of local speleothems were able to record multiannual isotopic changes inherited from stable isotopes in the drip water. CO 2 concentration showed seasonality (high values in summer and low values in winter) in both caves, likely affecting carbonate precipitation or corrosion and consequently stalagmite growth. Systematic variations among Mg/Ca and Sr/Ca, Na/Ca, and Si/Ca element ratios were detected in the drip water suggesting Prior Calcite Precipitation (PCP). As PCP is characteristic of periods of reduced infiltration during drier weather conditions, the variations in drip water chemistry and drip rates indicate that the hydrological conditions also varied significantly during the studied period. This hydrological variability appears to affect not only trace element composition but also the isotopic composition of modern carbonate precipitates. In summary, these findings imply that the speleothems from the studied caves were able to record the hydrological changes resulting from alternating wet and dry periods, and therefore the geochemical data can be used to reconstruct past climate and environmental changes.
Development of peptide-based conjugates for targeted tumour therapy is a current research topic providing new possibilities in cancer treatment. In this study, VHLGYAT heptapeptide selected by phage display technique for HT-29 human colon cancer was investigated as homing peptide for drug delivery. Daunomycin was conjugated to the N-terminus of the peptide directly or through Cathepsin B cleavable spacers. Conjugates showed moderate in vitro cytostatic effect. Therefore, sequence modifications were performed by Ala-scan and positional scanning resulting in conjugates with much higher bioactivity. Conjugates in which Gly was replaced by amino acids with bulky apolaric side chains provided the best efficacy. The influence of the cellular uptake, stability and drug release on the anti-tumour activity was investigated. It was found that mainly the difference in the cellular uptake of the conjugates generated the distinct effect on cell viability. One of the most efficient conjugate Dau=Aoa-LRRY-VHLFYAT-NH 2 showed tumour growth inhibition on orthotopically developed HT-29 colon cancer in mice with negligible toxic side effect compared to the free drug. We also indicate that this sequence is not specific to HT-29 cells, but it has a remarkable effect on many other cancer cells. Nevertheless, the Phe-containing conjugate was more active in all cases compared to the conjugate with the parent sequence. The literature data suggested that this sequence is highly overlapped with peptides that recognize Hsp70 membrane bound protein overexpressed in many types of tumours.
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