Eph receptors and their ligands: Promising molecular biomarkers and therapeutic targets in prostate cancer

Although at present, there is a high incidence of prostate cancer, particularly in the Western world, mortality from this disease is declining and occurs primarily only from clinically significant late stage tumors with a poor prognosis. A major current focus of this field is the identification of new biomarkers which can detect earlier, and more effectively, clinically significant tumors from those deemed “low risk”, as well as predict the prognostic course of a particular cancer. This strategy can in turn offer novel avenues for targeted therapies. The large family of Receptor Tyrosine Kinases, the Ephs, and their binding partners, the ephrins, has been implicated in many cancers of epithelial origin through stimulation of oncogenic transformation, tumor angiogenesis, and promotion of increased cell survival, invasion and migration. They also show promise as both biomarkers of diagnostic and prognostic value and as targeted therapies in cancer. This review will briefly discuss the complex roles and biological mechanisms of action of these receptors and ligands and, with regard to prostate cancer, highlight their potential as biomarkers for both diagnosis and prognosis, their application as imaging agents, and current approaches to assessing them as therapeutic targets. This review demonstrates the need for future studies into those particular family members that will prove helpful in understanding the biology and potential as targets for treatment of prostate cancer.     

The role of selected tree species in industrial sewage sludge/flotation tailing management

The aim of the study was to estimate the ability of ten tree and bush species to tolerate and accumulate Cd, Cu, Pb, Zn, and As species [As(III), As(V), and total organic arsenic] in industrial sewage sludge extremely contaminated with arsenic (almost 27.5 g kg^?1) in a pot experiment. The premise being that it will then be possible to select the most promising tree/bush species, able to grow in the vicinity of dams where sewage sludge/flotation tailings are used as landfill. Six of the ten tested tree species were able to grow on the sludge. The highest content of total As was observed in Betula pendula roots (30.0 ± 1.3 mg kg^?1 DW), where the dominant As species was the toxic As(V). The highest biomass of Quercus Q1 robur (77.3 § 2.6 g) and Acer platanoides (76.0 § 4.9 g) was observed. A proper planting of selected tree species that are able to thrive on sewage sludge/flotation tailings could be an interesting and promising way to protect dams. By utilizing differences in their root systems and water needs, we will be able to reduce the risk of fatal environmental disasters.     

Effect of extrusion on the nutritional value of peas for broiler chickens

The study was conducted to investigate the nutritional value of five samples of raw and extruded pea seeds (Pisum sativum L., Tarachalska cv.) from different experimental fields. The study included 150 male 1-day-old Ross 308 chickens, which were randomly assigned to three dietary treatments (50 replications each) and kept in individual cages. From days 1 to 16, all birds received only the basal diets. From days 17 to 21, the control group received still the basal diet, but for the two other groups, 20% of basal diet was replaced by raw or extruded peas. Furthermore, the groups receiving raw or extruded peas were divided into five subgroups of 10 animals each, where the diets contained one of the five pea samples of the same cultivar grown at different locations, respectively. On days 19 and 20, excreta were individually collected, and then all chickens were sacrificed and ileal digesta were sampled for determination of ileal digestibility, which was calculated by the difference method. Extrusion of pea seeds decreased the contents of crude fibre, acid and neutral detergent fibre, trypsin inhibitor activity (TIA), phytic P and resistant starch (RS) (p ≤ 0.05), but increased the contents of apparent metabolisable energy (AME_N) by approximately 2.25 MJ/kg dry matter (DM). Furthermore, extrusion improved the DM and crude protein digestibility significantly by about 21.3% and 11.6%, respectively. Similar results were observed for the digestibility of all analysed amino acids. In conclusion, extrusion markedly influenced the chemical composition of peas, reduced their contents of phytic P, TIA and RS and consequently had a positive impact on nutrient digestibility and AME_N values.     

Conformational control through translocational regulation: a new view of secretory and membrane protein folding

We suggest a new view of secretory and membrane protein folding that emphasizes the role of pathways of biogenesis in generating functional and conformational heterogeneity. In this view, heterogeneity results from action of accessory factors either directly binding specific sequences of the nascent chain, or indirectly, changing the environment in which a particular domain is synthesized. Entrained by signaling pathways, these variables create a combinatorial set of necessary-but-not-sufficient conditions that enhance synthesis and folding of particular alternate, functional, conformational forms. We therefore propose that protein conformation is productively regulated by the cell during translocation across the endoplasmic reticulum (ER), a concept that may account for currently poorly understood aspects of physiological function, natural selection, and disease pathogenesis.     

Development of a bioartificial nerve graft. II. Nerve regeneration in vitro

A promising alternative for the repair of peripheral nerve injuries is the bioartificial nerve graft, or BNG, comprised of a tubular conduit preseeded with Schwann cells, which are an effective substrate for enhancing nerve regeneration. The physical properties of the conduit, porosity and wall thickness, as well as the Schwann cell seeding density, were tested for their effect on axon growth using rat dorsal root ganglia. These parameters can influence the amount of nutrients and growth factors made available to the neural tissue. Results show that a greater wall thickness and lower porosities have a detrimental effect on the growth of the axons. Over a four week period, axons extended 3.2 mm for the optimum case (DeltaR = 0.82 mm, epsilon = 0.75) compared to 1.8 and 1.6 mm for a lower porosity (0.55) and a greater wall thickness (1.4 mm), respectively. A maximum in the growth rate occurs at a porosity of 75% for Schwann cell seeded conduits but not for unseeded ones. When compared to mass transfer predictions, the results suggest that, at higher porosities, more growth factors diffuse out of the conduit, while at low porosities there is competition for nutrients. Increasing the Schwann cell seeding density enhances growth but also leads to an increase in the number of axons along the length of the conduit. This is indicative of branching of the axons, which requires additional resources to maintain and can lead to painful neuroma formation. Wall thickness and porosity were found not to have any significant effect on the axon number sprouting from the dorsal root ganglia and the mean diameter (p > 0.05). Considerations need to be made, not just on the polymer used, but also on its porosity, wall thickness, and Schwann cell seeding density. These parameters can be adjusted to create a bioartificial nerve graft that provides the optimal environment for nerve growth.