Structure elucidation and biosynthesis of lysine-rich cyclic peptides in Xenorhabdus nematophila

Thirteen novel PAX (peptide-antimicrobial-Xenorhabdus) peptides were identified in Xenorhabdus nematophila HGB081. Their structures including the absolute configuration were elucidated using a combination of labeling experiments, detailed MS/MS experiments, the advanced Marfey's method, and a detailed analysis of the biosynthesis gene cluster, which was identified as well.     

Antiproliferative activity of chelating N,O- and N,N-ruthenium(II) arene functionalised poly(propyleneimine) dendrimer scaffolds

Chelating neutral (N,O) and cationic (N,N) first- and second-generation ruthenium(II) arene metallodendrimers based on poly(propyleneimine) dendrimer scaffolds were obtained from dinuclear arene ruthenium precursors by reactions with salicylaldimine and iminopyridyl dendritic ligands, respectively. The N,N cationic complexes were isolated as hexafluorophosphate salts and were characterised by NMR and IR spectroscopy, and MALDI-TOF mass spectrometry. Related mononuclear complexes were obtained in a similar manner and their molecular structures have been determined by X-ray diffraction analysis. The cytotoxicities of the mono- and multinuclear complexes were established using A2780 and A2780cisR human ovarian carcinoma cancer cell lines.     

Metabolite profiling and antioxidant activity of Prunus padus L. flowers and leaves

Six phenolics were obtained from the leaves of Prunus padus by activity-guided isolation: isorhamnetin 3-O-β-xylopyranosyl-(1?→?2)-β-galactopyranoside (1), astragalin (2), hyperoside (3), quercetin 3-O-β-xylopyranosyl-(1?→?2)-β-galactopyranoside (4), quercetin 3-O-β-xylopyranosyl-(1?→?2)-β-glucopyranoside (5) and chlorogenic acid (6). The antioxidant potential of 70% methanolic extracts from the flowers and leaves collected over the growing season was evaluated using the 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging and 2,2′-azobis-(2-amidinopropane) dihydrochloride (AAPH)-induced linoleic acid (LA) peroxidation tests in relation to the contents of the isolates 1-6, total phenolics, total proanthocyanidins and total quercetin. The IC?? values were expressed in gram dry weight per gram of DPPH or LA, respectively, and were in the range of 1.42-2.42 for the DPPH test and 1.78-4.92 for the LA peroxidation, with superior activity found for the flowers and the autumn leaves. Significant linear correlation of these values to the sum of proanthocyanidins and compounds 1-6 (R2?>?0.87) showed that the listed phenolics are synergists of the tested activity.     

Synthesis, characterisation and in vitro anti-angiogenic potential of dendron VEGF blockers

To overcome the lack of in vivo stability of certain peptides used in cancer treatment and to increase their retention time in the extracellular matrix of the target tissue, the anti-angiogenic WHLPFKC sequence is synthesised at the uppermost branching generation of a poly(ε-lysine) dendron. The root of these dendrons is designed to interact preferentially with macromolecules of the extracellular matrix, whilst the uppermost branching generation of the dendron increased the exposed density of the bioactive peptide. Bioactivity testing of the blockers is performed on HUVECs. The results show that the dendron tethered with VEGF blockers was still able to inhibit proliferation and angiogenesis. Their relatively larger structure did not prevent the interaction with VEGF.     

Baltimore PM2.5 Supersite: highly time-resolved organic compounds—sampling duration and phase distribution—implications for health effects studies

As part of the Baltimore PM2.5 Supersite study, intensive three-hourly continuous PM2.5 sampling was conducted for nearly 4 weeks in summer of 2002 and as well in winter of 2002/2003. Close to 120 individual organic compounds have been quantified separately in filter and polyurethane foam (PUF) plug pairs for 17 days for each sampling period. Here, the focus is on (1) describing briefly the new sampling system, (2) discussing filter/PUF plugs breakthrough experiments for semi-volatile compounds, (3) providing insight into phase distribution of semi-volatile organic species, and (4) discussing the impact of air pollution sampling time on human exposure with information on maximum 3- and 24-h averaged ambient concentrations of potentially adverse health effects causing organic pollutants. The newly developed sampling system consisted of five electronically controlled parallel sampling channels that are operated in a sequential mode. Semi-volatile breakthrough experiments were conducted in three separate experiments over 3, 4, and 5 h each using one filter and three PUF plugs. Valuable insight was obtained about the transfer of semi-volatile organic compounds through the sequence of PUF plugs and a cut-off could be defined for complete sampling of semi-volatile compounds on only one filter/PUF plug pair, i.e., the setup finally used during the seasonal PM2.5 sampling campaign. Accordingly, n-nonadecane (C19) with a vapor pressure (vp) of 3.25 × 10⁻⁴ Torr is collected with > 95% on the filter/PUF pair. Applied to phenanthrene, the most abundant the PAH sampled, phenanthrene (vp, 6.2 × 10⁻⁵ Torr) was collected completely in wintertime and correlates very well with three-hourly PM2.5 ambient concentrations. Valuable data on the fractional partitioning for semi-volatile organics as a function of season is provided here and can be used to differentiate the human uptake of an organic pollutant of interest via gas- and particle-phase exposure. Health effects studies often relay on PM2.5 exposure measurements taken over 24 h or longer. We found that maximum 3-h concentrations are frequently two to five times higher than that found for maximum 24-h concentrations, an important aspect when considering that short-term exposure to higher air pollution levels are more likely to overpower defense mechanisms in the human lung with subsequent adverse effects even at lower pollutant levels.     

Extending the applicability of pressurized hot water extraction to compounds exhibiting limited water solubility by pH control: curcumin from the turmeric rhizome

Pressurized hot water extraction (PHWE, also known as subcritical water extraction) is commonly considered to be an environmentally friendly extraction technique that could potentially replace traditional methods that use organic solvents. Unfortunately, the applicability of this technique is often limited by the very low water solubility of the target compounds, even at high temperatures. In this paper, the scope for broadening the applicability of PHWE by adjusting the pH of the water used in the extraction is demonstrated in the extraction of curcumin (which exhibits very limited water solubility) from untreated turmeric (Curcuma longa L.) rhizomes. Although poor extraction yields were obtained, even at high temperatures when using degassed water or neutral phosphate buffer as the extraction medium, yields exceeding those obtained by Soxhlet extraction were achieved using highly acidic pH buffers due to curcumin protonation. The influence of the temperature, pH, and buffer concentration on the extraction yield were investigated in detail by means of a series of designed experiments. Optimized conditions for the extraction of curcumin from turmeric by PHWE were estimated at 197 °C using 62 g/L buffer concentration at pH 1.6. The relationships between these variables were subjected to statistical analysis using response surface methodology.     

Shotgun proteomic analytical approach for studying proteins adsorbed onto liposome surface

The knowledge about the interaction between plasma proteins and nanocarriers employed for in vivo delivery is fundamental to understand their biodistribution. Protein adsorption onto nanoparticle surface (protein corona) is strongly affected by vector surface characteristics. In general, the primary interaction is thought to be electrostatic, thus surface charge of carrier is supposed to play a central role in protein adsorption. Because protein corona composition can be critical in modifying the interactive surface that is recognized by cells, characterizing its formation onto lipid particles may serve as a fundamental predictive model for the in vivo efficiency of a lipidic vector. In the present work, protein coronas adsorbed onto three differently charged cationic liposome formulations were compared by a shotgun proteomic approach based on nano-liquid chromatography–high-resolution mass spectrometry. About 130 proteins were identified in each corona, with only small differences between the different cationic liposome formulations. However, this study could be useful for the future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins into body fluids.     

Multi-walled carbon nanotubes–dispersive solid-phase extraction combined with nano-liquid chromatography for the analysis of pesticides in water samples

In this work, the simultaneous separation of a group of 12 pesticides (carbaryl, fensulfothion, mecoprop, fenamiphos, haloxyfop, diclofop, fipronil, profenofos, fonofos, disulfoton, nitrofen, and terbufos) by nano-liquid chromatography with UV detection is described. For the analyses, a 100 μm internal diameter capillary column packed with silica modified with phenyl groups was used. Experimental parameters, including the use of a trapping column for increasing the sensitivity, were optimized and validated. A preliminary study of the applicability of a rapid and practical dispersive solid-phase extraction (DSPE) procedure was developed for the extraction of some of these pesticides (carbaryl, fensulfothion, fenamiphos, fipronil, profenofos, fonofos, disulfoton, nitrofen, and terbufos) from Milli-Q water samples using multi-walled carbon nanotubes (MWCNTs). The method was validated through a recovery study at three different levels of concentration, obtaining limits of detection in the range 0.016–0.067 μg/L (below European Union maximum residue limits) for the majority of the pesticides. In this work, MWCNTs were reused up to five times, representing an important reduction of the waste of stationary phase. Furthermore, DSPE permitted a clear diminution of the total sample treatment time with respect to conventional SPE.     

Discounted dynamic programming with unbounded returns: Application to economic models

In this paper, we study discounted Markov decision processes on an uncountable state space. We allow a utility (reward) function to be unbounded both from above and below. A new feature in our approach is an easily verifiable rate of growth condition introduced for a positive part of the utility function. This assumption, in turn, enables us to prove the convergence of a value iteration algorithm to a solution to the Bellman equation. Moreover, by virtue of the optimality equation we show the existence of an optimal stationary policy.