Effect of temperature on the interaction of cisplatin with the model protein hen egg white lysozyme

The products of the reaction between cisplatin (CDDP) and the model protein hen egg white lysozyme (HEWL) at 20, 37 and 55 °C in pure water were studied by UV–Vis absorption spectroscopy, intrinsic fluorescence and circular dichroism, dynamic and electrophoretic light scattering and inductively coupled plasma mass spectrometry. X-ray structures were also solved for the adducts formed at 20 and 55 °C. Data demonstrate that high temperature facilitates the formation of CDDP-HEWL adducts, where Pt atoms bind ND1 atom of His15 or NE2 atom of His15 and NH1 atom of Arg14. Our study suggests that high human body temperature (fever) could increase the rate of drug binding to proteins thus enhancing possible toxic side effects related to CDDP administration.     

Characterization of discrete and continuous modes of visual pattern discrimination

Discrete and continuous modes of visual pattern discrimination performance are analyzed using a model for the investigation of discrete internal pattern representations described in previous papers (Foster, 1980a, b). A simple quantitative criterion is derived to characterize the two kinds of visual discrimination performance. Values predicted by this criterion are then compared with values obtained from experimental data.     

Acute Toxicity of water-borne dimethylnitrosamine (DMN) to Fundulus heteroclitus (L.)

Acute (120h) toxicity of the water-borne carcinogen, dimethylnitrosamine (DMN) to adult Fundulus heteroclitus (L.) at 20°C and 20.2%₀ salinity in natural seawater was determined. The LC-50 values were 8300 mg/1 at 24 h, 5500 mg/1 at 48 h, 4700 mg/1 at 72 h, 3300 mg/1 at 96 h and 2700 mg/1 at 120 h.
Gross lesions consisted of peritoneal and cephalic ecchymoses. Microscopic lesions included necrosis and sloughing of the gastrointestinal mucosa, haemorrhage and necrosis of the liver, and necrosis of taste buds, with severity and incidence being a function of DMN concentration. Acute pathological effects of DMN on Fundulus heteroclitus conformed closely to those reported in other species exposed to this compound by respiratory, oral or parenteral route. DMN concentrations used in this experiment greatly exceeded those expected to be found under natural conditions, and this report is intended both to improve our understanding of DMN-induced pathology in marine fishes and to provide further evidence of the consistency of acute lesions induced by DMN, regardless of test organism or mode of exposure.     

Stress proteins by zinc ions in sea urchin embryos

In Paracentrotus lividus embryos, treatment with zinc ions induces the synthesis of the two major stress proteins with the same molecular weight as those induced by heat shock. The developmental stages responsive to zinc ion treatment are the same as those responsive to heat shock. However, zinc treatment induces a longer lasting synthesis of the stress proteins, and, unlike heat shock, does not induce thermotolerance and does not inhibit synthesis of the bulk proteins.     

Making parks make a difference: poor alignment of policy,planning and management with protected-area impact,and ways forward

Policy and practice around protected areas are poorly aligned with the basic purpose of protection, which is to make a difference. The difference made by protected areas is their impact, defined in program evaluation as the outcomes arising from protection relative to the counterfactual of no protection or a different form of protection. Although impact evaluation of programs is well established in fields such as medicine, education and development aid, it is rare in nature conservation. We show that the present weak alignment with impact of policy targets and operational objectives for protected areas involves a great risk: targets and objectives can be achieved while making little difference to the conservation of biodiversity. We also review potential ways of increasing the difference made by protected areas, finding a poor evidence base for the use of planning and management ‘levers’ to better achieve impact. We propose a dual strategy for making protected areas more effective in their basic role of saving nature, outlining ways of developing targets and objectives focused on impact while also improving the evidence for effective planning and management.     

Diuretic activity of an aqueous extract of Phyllanthus sellowianus.

Phyllanthus sellowianus Muell. Arg. (Euphorbiaceae) is used widely as a hypoglycemic and diuretic agent in South American folk medicine. In order to assess the diuretic activity of this plant, test animals were treated with a single oral administration of an aqueous extract (5% w/v) of the stem bark of P. sellowianus (400 mg/kg body weight), which produced after 8 h a significant increase in the urinary excretion. In the studies on acute toxicity in mice neither mortality nor neurobehavioral or autonomic profile changes could be observed.     

Synthesis, conformation, receptor binding and biological activities of monobiotinylated human insulin-like peptide 3.

Biotin-avidin immobilization has been routinely used as a tool to study peptide-receptor and peptide-antibody interactions. Biotinylated peptides can also be employed to localize cells that express the peptides' receptor, and to analyse ligand-receptor binding. Insulin-like peptide 3 (INSL3) is a peptide hormone which contains A- and B-chains connected by two disulphide bonds and plays a role in testicular descent during sexual development. In order to study the interaction of INSL3 with its receptor LGR8, a G protein-coupled receptor, we chemically synthesized Nalpha-mono-biotinylated human INSL3 (B-hINSL3) and compared it structurally and biologically with hINSL3. Both peptides exhibited similar, but high, receptor binding affinities on human foetal kidney fibroblast 293T cells transfected human LGR8 based on a competition radioreceptor assay with 33P-labelled relaxin H2 (B33). The modified B-hINSL3 showed full biological activity as determined by the stimulation of gubernacular cell proliferation. The labelled B-hINSL3 contains a higher alpha-helix content, and this increased helical structure is accompanied by an increase in ability to stimulate cAMP accumulation in 293T cells expressing LGR8. Our results suggest that the N-terminal region of the A-chain is not involved in the interaction of INSL3 with its receptor. However, the introduction of biotin onto the N-terminus of the A-chain promoted conformational stability which, in turn, permitted better receptor activation.