Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl(2)(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η(6)-bip)Os(4-CO(2)-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η(6)-p-cym)RuCl(dap)](+) (p-cym = p-cymene) (5), and [(η(6)-p-cym)RuCl(imidazole-CO(2)H)(PPh(3))](+) (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC(50) = 63 ± 2 μM in MCF-7 cells and IC(50) = 26 ± 3 μM in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC(50) = 45 ± 2.6 μM in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically.     

Anatomy of the coracoid and diversity of the Procellariiformes (Aves) in the Oligocene of Europe

Abstract: Two European species of the Diomedeoididae, an extinct family of procellariiform (tube‐nose) birds, have hitherto been distinguished primarily by size of their limb bones. Here, we describe an Early Oligocene (Rupelian) procellariifom coracoid that in all probability represents the larger species, Diomedeoides lipsiensis, and compare it to the coracoids of smaller diomedeoidids and extant procellariiforms. Using multivariate (Principal Component Analysis) and univariate analyses, we demonstrate that nearly all measurements are heavily size dependent, which makes the proportions and some other shape characters of little use as phylogenetic markers. Among eight measurements, the coracoid corpus width shows the highest correlation (higher than corpus depth) with body mass, permitting a precise calculation of over twofold difference in body mass between D. lipsiensis and smaller species. Among 16 qualitative characters analysed, the majority proved too variable to be used as markers of interfamily relationships and only 2–3, the ventral intermuscular line, sternocoracoid articulation (divided vs. undivided), and, with reservations, epimarginal crest vary consistently between the families. By far the most variable is the acrocoracoid process that tends to be deeper (more elongate dorsoventrally) in larger petrels but not in the albatrosses. However, the detailed shapes of the acrocoracoid heads are highly genus specific and suggest a genus‐level diversity among the Diomedeoididae from the Oligocene of Europe. The common features of the diomedeoidid coracoids are best interpreted as plesiomorphies, which accounts for some similarities to the Oceanitinae (that are probably basal among the crown‐group procellariiforms). The evidence from the coracoid is consistent with a stem‐group position of the Diomedeoididae as previously proposed by others. We emphasize the need of a group‐specific character analysis, primarily of allometries and levels of character variation, prior to a phylogenetic reconstruction.     

Primary coronary intervention for ST-elevation myocardial infarction in Indonesia and the Netherlands: a comparison

Background. Although the beneficial effects of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) have been demonstrated in a number of trials, most studies were conducted in Western countries. Experience, logistics and patient characteristics may differ in other parts of the world. Methods. Consecutive patients treated with primary PCI in Cinere Hospital, Jakarta, Indonesia, between January 2008 and October 2008 were compared with those treated in the Isala Clinics, Zwolle, the Netherlands. Results. During the study period, a total of 596 patients were treated by primary PCI, 568 in Zwolle and 28 in Jakarta. Patients in Indonesia were younger (54 vs 63 years), more often had diabetes (36 vs. 12%) and high lipids and were more often smokers (68 vs. 31%). Time delay between symptom onset and admission was longer in Indonesia. Patients from Indonesia more often had signs of heart failure at admission. The time between admission and balloon inflation was longer in Indonesia. At angiography, patients from Indonesia more often had multivessel disease. There was no difference in the percentage of restoration of TIMI 3 flow by primary PCI between the two hospitals. Conclusion. Patients with STEMI in Indonesia have a higher risk profile compared with those in the Netherlands, according to prevalence of coronary risk factors, signs of heart failure, multivessel disease and patient delay. Time delay between admission and balloon inflation was much longer in Indonesia, because of both logistic and financial reasons. (Neth Heart J 2009;17:418–21.)     

Efficient hydrogen production from the lignocellulosic energy crop Miscanthus by the extreme thermophilic bacteria Caldicellulosiruptor saccharolyticus and Thermotoga neapolitana

Background  

The production of hydrogen from biomass by fermentation is one of the routes that can contribute to a future sustainable hydrogen economy. Lignocellulosic biomass is an attractive feedstock because of its abundance, low production costs and high polysaccharide content.     

Crop rotation and tillage systems as a proactive strategy in the control of peanut fungal soilborne diseases

Soil management practices can affect the population dynamics of soil microbial communities. Cultural practices can be adequately combined to benefit natural populations of microorganisms that may have a role in biological control (actinomycetes, Trichoderma spp., and Gliocladium spp.), thus contributing to the management of peanut fungal soilborne diseases in a sustainable manner within ecological boundaries. During six agricultural cycles, rhizosphere soil samples were taken from a field subjected to crop rotation (soybean, peanut, and maize), peanut being under two tillage systems (no till, reduced tillage) with the aim of quantifying populations of soil microorganisms. The incidence of diseases caused by soilborne fungi in peanut was determined at harvest. The highest amount of actinomycetes, Trichoderma spp., and Gliocladium spp. were recorded when maize was the preceding crop. Regarding tillage systems, the populations of the three groups of microorganisms were higher in peanut under no tillage than under reduced tillage. Under these conditions, the lowest incidence of peanut blight (Sclerotinia minor) and root rot (strains of Fusarium solani) was observed, suggesting a possible natural control of peanut soilborne pathogens. The quantification of actinomycetes, Trichoderma spp., and Gliocladium spp. was used as a tool to explore the impacts of different management systems on microbial groups that may be involved in the biological control of soilborne diseases, with the aim of combining those practices that improve native populations of possible beneficial microorganisms. This manipulation can provide sustainable management strategies in the control of soilborne diseases, avoiding the use of artificial inoculations of microorganisms, and reducing agrochemical application.     

EspJ of enteropathogenic and enterohaemorrhagic Escherichia coli inhibits opsono-phagocytosis

A key strategy in microbial pathogenesis is the subversion of the first line of cellular immune defences presented by professional phagocytes. Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC respectively) remain extracellular while colonizing the gut mucosa by attaching and effacing mechanism. EPEC use the type three secretion system effector protein EspF to prevent their own uptake into macrophages. EPEC can also block in trans the internalization of IgG-opsonized particles. In this study, we show that EspJ is the type three secretion system effector protein responsible for trans -inhibition of macrophage opsono-phagocytosis by both EPEC and EHEC. While EspF plays no role in trans -inhibition of opsono-phagocytosis, espJ mutants of EPEC or EHEC are unable to block uptake of opsonized sheep red blood cells (RBC), a phenotype that is rescued upon complementation with the espJ gene. Importantly, ectopic expression of EspJ^EHEC in phagocytes is sufficient to inhibit internalization of both IgG- and C3bi-opsonized RBC. These results suggest that EspJ targets a basic mechanism common to these two unrelated phagocytic receptors. Moreover, EspF and EspJ target independent aspects of the phagocytic function of mammalian macrophages in vitro .     

A morphological and genetic analysis of the European bitterling species complex

Bitterling fishes lay their eggs on the gills of living freshwater mussels and are valuable models in behavioural and evolutionary ecology. We used morphological and genetic data to resolve the taxonomic relationships of bitterling in Europe. Previous studies have suggested the European bitterling is either a single species with a wide but discontinuous geographic distribution, or a complex of species. Morphometric and meristic data identified differences between three putative species; with a clear distinction between the eastern Asian Rhodeus sericeus, western European bitterling Rhodeus amarus, and colchian bitterling, Rhodeus colchicus. Polymorphism in the mitochondrial DNA control region was predominantly due to insertion/deletion events, making phylogenetic inference difficult, but the single haplotype found in R. sericeus populations was detected at low frequency (one of 24 individuals) in R. amarus and R. colchicus populations. Eight control region haplotypes were found in R. amarus populations, which were distinct from the two haplotypes in a R. colchicus population. Cytochrome b data produced a phylogeny with strongly‐supported differentiation between a clade of two R. sericeus haplotypes and a clade of six R. amarus/colchicus haplotypes. The star‐like topology of the R. amarus/colchicus haplotypes in a minimum spanning network suggested a rapid radiation in this clade. Our results are consistent with an hypothesis of relatively ancient divergence of R. sericeus from R. amarus/colchicus and more recent and rapid differentiation between R. amarus and R. colchicus. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 95 , 337–347.     

Determination of phytic acid by gas chromatography–mass spectroscopy: application to biological samples

A GC–MS method is reported for the determination of phytic acid based on purification by anion-exchange chromatography, enzymatic hydrolysis of phytic acid to myo-inositol and derivation to trimethylsilyl derivative, with scyllo-inositol as an internal standard. Analytical features of the method are: limit of detection 9 μg l⁻¹ phytic acid, linear working range 18–500 μg l⁻¹ phytic acid, and coefficient of variation 1.9%. The method has been successfully applied to a variety of biological samples: various rat organs (kidney, liver, brain and bone), human plasma and urine and kidney stones. A comparative study of sample treatments, including deproteization, lipid extraction and the presence of a chelator, is also reported. Phytic acid amounts found in rat organs ranged from 1.07 g kg⁻¹ for bone to 32.0 g kg⁻¹ for brain. Phytic acid in human plasma was of the order of 0.14 mg l⁻¹. In kidney stones, phytic acid was found in calcium containing stones.     

Vascular ligation response is independent of p107: stressing the role of the related p130

Recent studies have revealed the role of the pRb family members pRb and p130 in the response to vascular injury. We evaluated the arterial injury response in the absence of p107, a protein that shares a high degree of homology with the injury-controlling p130. Carotid artery ligation and perivascular electric injury of the femoral artery were applied to p107 knockout (p107 -/-) mice, and morphometric analysis was performed 3 wk after ligation and electric injury. Arterial vessels of p107 -/- mice were indistinguishable from controls under basal conditions. After carotid artery ligation the p107 -/- mice (n = 7) did not display an enhanced ligation response compared with controls (n = 9), which was studied over a distance of approximately 450 microm proximal and approximately 200 microm distal from the ligation site, with regard to vessel wall area, neointima area, and lumen area. Corresponding with this, morphometric data obtained from the perivascular electric injury of the femoral artery confirmed the lack of enhanced ligation and injury response in the absence of p107. We conclude that the pRb family member p107 is not a key regulator in vascular injury response. These data, in conjunction with previously reported results, indicate that the control of vascular injury response is not a redundant feature of pRb proteins but primarily specific for p130. Further studies on functional domains of p130 and p107 will help to resolve the pathways in vascular injury response.