Radioisotope therapy with somatostatin analogues in neuroendocrine tumours (case report)

Restricted number of neuroendocrine tumors (NET) shows overexpression of somatostatin receptors. Therefore, long-acting somatostatin analogues are used in diagnosis and treatment of those tumors. Here we present our first case of NET, localized in pancreas treated with DOTA-D-Phe 1-Tyr 3-octreotide (DOTATATE), for receptor-mediated radioisotope therapy. DOTATATE is a newly developed somatostatin analogue labeled with beta-emitter yttrium 90 (90Y) and beta, gamma-emitter lutetium 177 (177Lu). A 34-year old woman was suffering from several years gastrointestinal symptoms. NET of the pancreas with multiple metastases into the liver was diagnosed based on histopatological, biochemical and radiological tests. First, she had chemiotherapy (leucovorin, 5-FU, cisplatin), however there was any positive effects of this therapy. Next, she received four single doses of 90Y DOTATATE at 4-6- week intervals, yielding a cumulative dose of 7.4 GBq/m2. During the 4th cycle the Lu-177 DOTATATE was additionally administered. As a renal protection i.v. infusion of amino acid solution were used during the treatment sessions. To date, patient has shown partial remission with reduction of tumor masses. We observed spectacular clinical, biochemical and radiological improvement. Radioisotope therapy could be a powerful and promising method of treatment at least in patients who had no other treatment option.     

The role of solid waste materials as habitats for macroinvertebrates in a lowland dam reservoir

Eight hypereutrophic phytoplankton dominated ponds from the Brussels Capital Region (Belgium) were biomanipulated (emptied with fish removal) to restore their ecological quality and reduce the risk of cyanobacterial bloom formation. Continuous monitoring of the ponds before and after the biomanipulation allowed the effects of the management intervention on different compartments of pond ecosystems (phytoplankton, zooplankton, submerged vegetation and nutrients) to be assessed. Fish removal resulted in a drastic reduction in phytoplankton biomass and a shift to the clear-water state in seven out of eight biomanipulated ponds. The reduction in phytoplankton biomass was associated with a marked increase in density and size of large cladocerans in six ponds and a restoration of submerged macrophytes in five ponds. The phytoplankton biomass in the ponds with extensive stands of submerged macrophytes was less affected by planktivorous fish recolonisation of some of the ponds later in the summer. The two non-vegetated ponds as well as one pond with sparse submerged vegetation showed a marked increase in phytoplankton biomass associated with the appearance of fish. Phytoplankton biomass increase coincided with the decrease in large Cladocera density and size. One pond lacking submerged macrophytes could maintain very low phytoplankton biomass owing to large Cladocera grazing alone. The results of this study confirmed the importance of large zooplankton grazing and revegetation with submerged macrophytes for the maintenance of the clear-water state and restoration success in hypereutrophic ponds. They also showed that large Cladocera size is more important than their number for efficient phytoplankton control and when cladocerans are large enough, they can considerably restrain phytoplankton growth, including bloom-forming cyanobacteria, even when submerged vegetation is not restored. The positive result of fish removal in seven out of eight biomanipulated ponds clearly indicated that such management intervention can be used, at least, for the short-term restoration of ecological water quality and prevention of noxious cyanobacterial bloom formation. The negative result of biomanipulation in one pond seems to be related to the pollution by sewage water. Guest editors: B. Oertli, R. Cereghino, A. Hull & R. Miracle Pond Conservation: From Science to Practice. 3rd Conference of the European Pond Conservation Network, Valencia, Spain, 14–16 May 2008     

Ultrascale and microscale growth dynamics of the cidaroid spine of Phyllacanthus imperialis revealed by 26Mg labeling and NanoSIMS isotopic imaging

Growth dynamics of the primary spine of the cidaroid sea urchin Phyllacanthus imperialis was assessed for the first time using pulsed ²⁶Mg‐labeling and NanoSIMS isotopic imaging. The sea urchin was incubated twice (for 48 h) in artificial seawater with elevated level of ²⁶Mg. After each labeling event, the sea urchin was returned for 72 h to seawater with natural isotopic abundance of ²⁶Mg. NanoSIMS ion microprobe was subsequently used to visualize the labeled regions of the spine with submicrometer lateral resolution. The growth of the new skeleton was restricted to the distalmost and peripheral portions of the spine. Skeletogenesis involved mostly the deposition of continuous thickening layers and lateral growth involving bridges between previously formed trabeculae. The timescale of formation of individual thickening layers (ca. 1 µm in width) on the stereom trabeculae was on the order of 1 day. Longitudinal growth occurred mainly at the periphery in the form of small portions of the thickening deposits or more massive microspines that appeared to branch and fuse with those above and below. These microspines were found to grow at about 10 µm/day. These results reveal that the skeletal growth of a juvenile cidaroid spine is complex and highly heterogeneous, with different extension rates depending on the stage of the stereom development and/or direction of the growth fronts. The growth pattern observed here at the submicrometer scale provides direct evidence supporting the earlier suggestions that the lamellar structure of echinoderm stereom is formed by periodic deposition of continuous mineral layers. J. Morphol. 275:788–796, 2014. © 2014 Wiley Periodicals, Inc.     

SNP-minisequencing as an excellent tool for analysing degraded DNA recovered from archival tissues

SNP-minisequencing has become common in forensic genetics, especially for analysing degraded or low copy number DNA (LCN DNA). The aim of this study was to examine the usefulness of five SNP (single nucleotide polymorphism) markers for analyzing degraded and LCN DNA recovered from archival samples. DNA extractions of eight formalin-fixed paraffin-embedded (FFPE) tissues were performed and DNA fragments were amplified in one multiplex PCR (polymerase chain reaction). SNPs were identified in a minisequencing reaction and a gel electrophoresis in ABI Prism 377 Sequencer. The research confirmed the usefulness of SNP-minisequencing for analysing FFPE tissues.     

Feeding preferences of an invasive Ponto‐Caspian goby for native and non‐native gammarid prey

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The usefulness of cyclic diamidines with different core-substituents as antitumor agents

A series of related polycationic compounds has been screened for potential antitumor activity by the NCI’s in vitro testing (one dose primary anticancer assay and the NCI-60 full panel screening). The GI₅₀ values of triazines 3 and 4 are on average 1.9 μM and 2.4 μM, respectively. Furan 8 deserves mention too (1.9 μM). The biological test results showed that carbazole 10 possessed cytotoxic activity in the nanomolar range, much better than the other compounds tested, only against several cancer cell lines: CCRF-CEM, HL-60(TB), MOLT-4, NCI-H522, COLO 205, SF-268, but the average GI₅₀ value was higher (15 μM). The activity appears closely dependent on the core-shape and length of the bisimidazoline molecules (important for both high cytotoxicity and DNA binding). The mechanism of DNA minor-groove binding of diamidines 1-12, based on the anticancer parameters, is highly probable.     

Palaeoecological evolution of a spring-fed fen in Pawłów (eastern Poland)

A continuous record of sedimentation in spring-fed fens makes them suitable for detailed palaeoenvironmental studies. A newly investigated cupola spring-fed fen (Paw?ów site), located in the Lublin chalkland, eastern Poland, was the object of our study. This special karst region is characterised by the occurrence of Upper Cretaceous carbonate rocks in the substratum. Sedimentological observations indicated strong variability of biogenic-carbonate series in the deposits (=peat-tufa rhythmite), reflects changes of accumulation conditions (oxidising versus reducing), resulting from alternate occurrence of warmer and cooler periods. Difficulties in pollen analysis due to oxidising conditions necessitate a multidisciplinary approach for palaeoenvironmental reconstruction. We used a multidisciplinary approach (sedimentological, palaeobotanical, geochemical analyses and radiocarbon dating) to determine the main evolutionary stages of this unique fen ecosystem and to discuss the role of local or/and regional factors in its development. Pollen and plant macrofossil analyses, supported by radiocarbon dating, proved that the bottom part of the cores represents the Late Glacial–Early Holocene stages of the fen development. A comparative analysis of palaeoenvironmental data showed close resemblance between the Paw?ów fen and the earlier studied fens in eastern Poland and Central-Eastern Europe, and the connection between their development and supraregional hydrological-climatic factors. The results indicated also the influence of the morphological position of such a type of ecosystem on the development of a continuous deposit succession. The occurrence of a river valley in close proximity of the Paw?ów site resulted in the lack of tufa deposits from the Atlantic period, because of an erosional phase in the river valley.     

Parallel selection mapping using artificially selected mice reveals body weight control loci

Understanding how polygenic traits evolve under selection is an unsolved problem, because challenges exist for identifying genes underlying a complex trait and understanding how multilocus selection operates in the genome. Here we study polygenic response to selection using artificial selection experiments. Inbred strains from seven independent long-term selection experiments for extreme mouse body weight ("high" lines weigh 42-77 g versus 16-40 g in "control" lines) were genotyped at 527,572 SNPs to identify loci controlling body weight. We identified 67 parallel selected regions (PSRs) where high lines share variants rarely found among the controls. By comparing allele frequencies in one selection experiment against its unselected control, we found classical selective sweeps centered on the PSRs. We present evidence supporting two G protein-coupled receptors GPR133 and Prlhr as positional candidates controlling body weight. Artificial selection may mimic natural selection in the wild: compared to control loci, we detected reduced heterozygosity in PSRs in unusually large wild mice on islands. Many PSRs overlap loci associated with human height variation, possibly through evolutionary conserved functional pathways. Our data suggest that parallel selection on complex traits may evoke parallel responses at many genes involved in diverse but relevant pathways.