Why phylogenetic signal of traits is important in ecosystems: uniformity of a plant trait increases soil fauna, but only in a phylogenetically uniform vegetation.

Phylogenetically closely related plant species often share similar trait states (phylogenetic signal), but local assembly may favor dissimilar relatives and thereby decouple the diversity of a trait from the diversity of phylogenetic lineages. Associated fauna might either benefit from plant trait diversity, because it provides them complementary resources, or suffer from it due to dilution of preferred resources. We hence hypothesize that decoupling of trait and phylogenetic diversity weakens the relationship between the plant-trait diversity and the abundance and diversity of associated fauna. Studying permanent meadows, we tested for combined effects of plant phylogenetic diversity and diversity of two functional traits (specific leaf area, leaf dry matter content) on major groups of soil fauna (earthworms, mites, springtails, nematodes). We found that only in phylogenetically uniform plant communities, was uniformity in the functional traits associated with (i) high abundance in springtails, and (ii) high abundance of the sub-group that feeds more directly on plant material (in springtails and mites) or those that are more prone to disturbance (in nematodes), and (iii) high diversity in all three groups tested (springtails, earthworms, nematodes). Our results suggest that soil fauna profits from the resource concentration in local plant communities that are uniform in both functional traits and phylogenetic lineages. Soil fauna would hence benefit from co-occurrence of closely related plants that have conserved the same trait values, rather than of distantly related plants that have converged in traits. This might result in faster decomposition and a positive feedback between trait conservatism and ecosystem functioning.

Noninvasive proteome analysis of psoriatic stratum corneum reflects pathophysiological pathways and is useful for drug profiling.

BACKGROUND: Protein expression is disturbed in the psoriatic stratum corneum (SC). Noninvasive methods for the description of pathophysiological changes and drug profiling in psoriasis are desirable. OBJECTIVES: Undertake large-scale noninvasive protein expression studies in psoriatic SC to identify biomarkers of pathophysiological processes and use them for drug profiling. METHODS: Psoriatic SC was harvested through repetitive tape-stripping. Nonlesional and lesional SC, as well as vehicle-treated and drug-treated lesional SC samples were collected. Protein extracts from nonlesional and lesional skin biopsies were used for comparison. Calcipotriol-betamethasone (CB) was used as a reference medication. Proteins extracted from pooled tape strips were quantified using mass spectrometry (MS), Western blotting, enzyme-linked immunosorbent assay and Luminex technologies. RESULTS: MS-based methods identified 140 proteins differentially expressed in psoriatic SC. Epidermis development, glycolysis, regulation of apoptosis, cytoskeleton organization and peptide cross-linking were modulated, all reflecting perturbed epidermal differentiation. Using antibody-based techniques, increased levels of sICAM1, of CXCL1- and CXCL8-attracting neutrophils, of CXCL10- and CCL4-attracting T helper (Th) 1 cells, and of CCL2- and CCL4-attracting monocytes and dendritic cells were observed. Quantification of the Th1 and Th17 markers tumour necrosis factor, interleukin (IL) 12B, IL17A and IL17F in lesional SC was successful, while the Th2 cytokines IL4, IL5 and IL13, not involved in the disease process, were not detected. The pruritic cytokine IL31 was detected in lesional SC. CXCL1, CXCL8, CXCL10 and sICAM were used to investigate disease remission, ranking three topical treatments according to their known clinical efficacy. CONCLUSIONS: Protein biomarker quantification in psoriatic SC detects key pathophysiological mechanisms and enables noninvasive drug profiling in translational medicine settings.

Detection of chemoresistance profile of cell lines K562, KB, GLC4 and HL60 through characterisation of the hmdr1, mrp and lrp transcripts.

The current trend in innovative cancer therapy is moving towards targeting the genes of interest by means of oligonucleotides developed for therapeutic or diagnostic use. These new approaches are of particular interest in oncology, and it would therefore be extremely useful to characterise all the biological tools currently available in this field. The chemoresistance profiles of four human cancer cell lines were determined by identifying of the operating conditions needed to characterise the presence of hmdr1, mrp and lrp mRNA by gene amplification.

Syntheses, structures, and properties of the bis(cyclopentadienyl) rare-earth imidodiphosphinochalocogenido compounds Cp2Ln[N(QPPh2)2] (Ln = La, Gd, Er, or Yb for Q = Se; Ln = Yb for Q = S).

The compounds Cp2Ln[N(QPPh2)2] (Ln = La (1), Gd (2), Er (3), or Yb (4) for Q = Se, Ln = Yb (5) for Q = S) have been synthesized from the corresponding rare-earth tris(cyclopentadienyl) compound and H[N(QPPh2)2]. The structures of compounds 1, 2, 3, and 5, as determined by X-ray crystallography, consist of a Cp2Ln fragment, coordinated eta 3 through two chalcogen atoms and an N atom of the imidodiphosphinochalcogenido ligand [N(QPPh2)2]-. In compound 4, the Cp2Yb moiety is coordinated eta 2 through the two Se atoms of the [N(SePPh2)2]-ligand. 31P and 77Se (for 1) NMR spectroscopies lend insight into the solution nature of these species. Crystal data: 1, C34H30LaNP2Se2, triclinic, P1, a = 9.7959(10) A, b = 12.4134(13) A, c = 13.9077(14) A, alpha = 88.106(2) degrees, beta = 88.327(2) degrees, gamma = 68.481(2) degrees, V = 1572.2(3) A3, T = 153 K, Z = 2, and R1(F) = 0.0257 for the 5947 reflections with I > .2 sigma(I); 2, C34H30GdNP2Se2, triclinic, P1, a = 9.7130(14) A, b = 12.2659(17) A, c = 13.953(2) A, alpha = 88.062(2) degrees, beta = 87.613(2) degrees, gamma = 69.041(2) degrees, V = 1550.7(4) A3, T = 153 K, Z = 2, and R1(F) = 0.0323 for the 5064 reflections with I > 2 sigma(I); 3, C34H30ErNP2Se2, triclinic, P1, a = 9.704(2) A, b = 12.222(3) A, c = 13.980(4) A, alpha = 88.230(4) degrees, beta = 87.487(4) degees, gamma = 69.107(4) degrees, V = 1547.4(7) A3, T = 153 K, Z = 2, and R1(F) = 0.0278 for the 6377 reflections with I > 2 sigma(I); 4, C34H30NP2Se2Yb.C4H8O, triclinic, P1, a = 12.087(4) A, b = 12.429(4) A, c = 23.990(7) A, alpha = 89.406(5) degrees, beta = 86.368(5) degrees, gamma = 81.664(5) degrees, V = 3558.8(18) A3, T = 153 K, Z = 4, and R1(F) = 0.0321 for the 11,883 reflections with I > 2 sigma(I); and 5, C34H30NP2S2Yb, monoclinic, P21/n, a = 13.8799(18) A, b = 12.6747(16) A, c = 17.180(2) A, beta = 91.102(3) degrees, V = 3021.8(7) A3, T = 153 K, Z = 4, and R1(F) = 0.0218 for the 6698 reflections with I > 2 sigma(I).

Soluble yttrium chalcogenides: syntheses, structures, and NMR properties of Y[eta 3-N(SPPh2)2]3 and Y[eta 2-N(SePPh2)2]2[eta 3-N(SePPh2)2].

The compounds Y[N(QPPh2)2]3 (Q = S (1), Se (2)) have been synthesized in good yield from the protonolysis reactions between Y[N(SiMe3)2]3 and HN(QPPh2)2 in methylene chloride (CH2Cl2). The compounds are not isostructural. In 1, the Y atom is surrounded by three similar [N(SPPh2)2]- ligands bound eta 3 through two S atoms and an N atom. The molecule possesses D3 symmetry, as determined in the solid state by X-ray crystallography and in solution by 89Y and 31P NMR spectroscopies. In 2, the Y atom is surrounded again by three [N(SePPh2)2]- ligands, but two are bound eta 2 through the two Se atoms and the other ligand is bound eta 3 through the two Se atoms and an N atom. Although a fluxional process is detected in the 31P and 77Se NMR spectra, a triplet is found in the 89Y NMR spectrum of 2 (delta = 436 ppm relative to YCl3 in D2O, 2JY-P = 5 Hz). This implies that on average the conformation of one eta 3- and two eta 2-bound ligands is retained in solution. Crystallographic data for 1: C72H60N3P6S6Y, rhombohedral, R3c, a = 14.927(5) A, c = 56.047(13) A, V = 10815(6) A3, T = 153 K, Z = 6, and R1(F) = 0.042 for the 1451 reflections with I > 2 sigma(I). Crystallographic data for 2: C72H60N3P6Se6Y.Ch2-Cl2, monoclinic, P2(1)n, a = 13.3511(17) A, b = 38.539(7) A, c = 14.108(2) A, beta = 94.085(13) degrees, V = 7241(2) A 3, T = 153 K, Z = 4, and R1(F) = 0.037 for the 8868 reflections with I > 2 sigma(I).

Comparison of conventional and synchrotron X-ray structure determinations of the adduct 1,2,4,5-tetrahydroxybenzene-2,5-dihydroxy-1,4-benzoquinone (1/1) and a conventional X-ray structure determination of 1,2,4,5-tetrahydroxybenzene monohydrate.

The X-ray structure of 1,2,4,5-tetrahydroxybenzene (benzene-1,2,4,5-tetrol) monohydrate, C6H6O4*H2O, (I), reveals columns of 1,2,4,5-tetrahydroxybenzene parallel to the b axis that are separated by 3.364 (12) and 3.453 (11) A. Molecules in adjacent columns are tilted relative to each other by 27.78 (8) degrees. Water molecules fill the channels between the columns and are involved in hydrogen-bonding interactions with the 1,2,4,5-tetrahydroxybenzene molecules. The crystal structure of the adduct 1,2,4,5-tetrahydroxybenzene-2,5-dihydroxy-1,4-benzoquinone (1/1), C6H6O4*C6H4O4, (II), reveals alternating molecules of 1,2,4,5-tetrahydroxybenzene and 2,5-dihydroxy-1,4-benzoquinone (both lying on inversion centers), and a zigzag hydrogen-bonded network connecting molecules in three dimensions. For compound (II), the conventional X-ray determination, (IIa), is in very good agreement with the synchrotron X-ray determination, (IIb). When differences in data collection temperatures are taken into account, even the displacement parameters are in very good agreement.

A new experimental model for studies of drug actions on myocardial metabolism. Application to a study of the influence of POCA.

In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.

Iodomethylated fatty acid metabolism in mice and dogs.

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono beta) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono beta into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.

Mathematical model of the metabolism of 123I-16-iodo-9-hexadecenoic acid in an isolated rat heart. Validation by comparison with experimental measurements.

The aim of the present study was to demonstrate that it is possible to estimate the intracellular metabolism of a fatty acid labelled with iodine using external radioactivity measurements. 123I-16-iodo-9-hexadecenoic acid (IHA) was injected close to the coronary arteries of isolated rat hearts perfused according to the Langendorff technique. The time course of the cardiac radioactivity was measured using an INa crystal coupled to an analyser. The obtained curves were analysed using a four-compartment mathematical model, with the compartments corresponding to the vascular-IHA (O), intramyocardial free-IHA (1), esterified-IHA (2) and iodide (3) pools. Curve analysis using this model demonstrated that, as compared to substrate-free perfusion, the presence of glucose (11 mM) increased IHA storage and decreased its oxidation. These changes were enhanced by the presence of insulin. A comparison of these results with measurements of the radioactivity levels within the various cellular fractions validated our proposed mathematical model. Thus, using only a mathematical analysis of a cardiac time-activity curve, it is possible to obtain quantitative information about IHA distribution in the different intracellular metabolic pathways. This technique is potentially useful for the study of metabolic effects of ischaemia or anoxia, as well as for the study of the influence of various substrates or drugs on IHA metabolism in isolated rat hearts.

Comparative effects of halothane associated with verapamil and ischaemia on myocardial metabolism in isolated perfused rat hearts.

The association of verapamil with halothane causes ischaemic-like myocardial dysfunction. Using an isolated rat heart model perfused with a radiolabelled fatty acid (123I-labelled iodohexadecenoic acid) as a sensitive marker of ischaemia this study investigated whether or not this dysfunction is of ischaemic origin. Hearts were perfused with a control solution or with solutions containing either 1% of halothane or 150 ng ml-1 of verapamil or the association of 0.75% halothane + 120 ng ml-1 verapamil. The ischaemic group was perfused at a reduced perfusion rate (-50%). Intracellular fate of IHA was assessed, and its esterification ratio computed. Ischaemia and the drugs induced a similar depression of haemodynamics. The esterification ratio in the ischaemic group was significantly higher (0.723 +/- 0.04) than in controls (0.0526 +/- 0.03) and than in the treated groups: halothane (0.533 +/- 0.06), verapamil (0.411 +/- 0.027) or the association halothane+verapamil (0.408 +/- 0.05), suggesting a non-ischaemic origin for the dysfunction caused by halothane-verapamil.

Assessment of iodohexadecenoic acid as a tracer of fatty acid metabolism by external detection: a study on isolated rat heart.

Labelled fatty acids have been proposed to explore cardiac metabolism. For the analysis of the external detection curve obtained with 16-iodo 9-hexadecenoic acid (IHA), we developed a mathematical 4-compartment model with compartments 0, 1, 2 and 3 representing vascular IHA, intracellular IHA, esterified forms and iodide, respectively. This model, used here for isolated rat hearts perfused in a recirculating system, is validated by an intracellular analysis, then tested in various metabolic conditions. Thus, the mathematical analysis of the external detection curve gives us numerical data on IHA metabolism, especially the distribution between degradation and storage. Our results confirm the suitability of IHA for assessing myocardial metabolism.

Kinetics of iodomethylated hexadecanoic acid metabolism in the rat myocardium: influence of the number and the position of methyl radicals.

The methyl-branched fatty acids, if radioiodine labelled in alpha position, are potentially adapted to a selective study of FA myocardial uptake. To determine the position and the number of methyl radicals that are necessary to obtain a maximal uptake and a minimal degradation, we measured time-activity evolution of isolated and perfused rat hearts after an injection of iodinated fatty acids which are mono- or dimethylated in alpha or beta position. Except for dimethyl fatty acid, the uptake is similar for all fatty acids studied to that of the straight chain analogue; beta mono- or dimethyl fatty acids seem best adapted to a study of the uptake because alpha monomethyl fatty acids undergo a metabolic degradation and alpha mono- and dimethyl fatty acids induce ventricular fibrillations.

Influence on the myocardial and blood activity course of the characteristics of the labelled fatty acid injected i.v. into mice.

In order to choose a labelled fatty acid (FA) for the external study of myocardial metabolism, FAs that are different in chain length, saturation, nature and position of the radioactive label, are injected i.v. into mice. Myocardial and blood activities are measured at various times p.i. It appears that hexadecanoic and hexadecenoic acids, iodine labelled in omega position, have the highest maximal myocardial activity among all the FAs studied. Furthermore, the myocardial and blood time-activity course is similar for both FAs. As unsaturated FAs have apparently a higher myocardial fixation in man than the saturated ones, 123I 16 iodo-9 hexadecenoic acid has been selected and seems well suited for the study of myocardial metabolism.

Kinetics of (16 123I) iodohexadecenoic acid metabolism in the rat myocardium, influence of glucose concentration in the perfusate and comparison with (1 14C) palmitate.

External counting, intracellular and subcellular distribution of (16 123I) iodohexadecenoic acid are studied on isolated rat hearts perfused with or without glucose. The presence of an exogenous substrate reduces the fatty acid oxidation and induces an increase of total cardiac and organic fraction activities. In this fraction, activity is very low for free fatty acids, but high for triglycerides and especially for polar lipids. The presence of an exogenous substrate leads to a more active esterification of fatty acids. Coronary effluents analysis shows, in the hydrophilic phase, a lower activity rebound in the presence of glucose. In the mitochondrial fraction, activity is mostly in the organic phase, as polar lipids especially. In the non-mitochondrial fraction, activity is much higher in the aqueous phase. 90 s p.i. of (l 14C) palmitic acid, over 80% of the myocardial activity is found in the hydrophilic fraction, which indicates--as for the iodo fatty acid (IHA)--an immediate and important oxidation, especially without glucose. These data seem to prove that IHA is taken up by the myocardial cells, enters the mitochondria where it is, without an early deiodination, oxidized with iodide release. IHA metabolic changes can be seen on the external detection myocardial activity curve. Omega iodinated fatty acids do not undergo a nonspecific important deiodination and are therefore well adapted to an external study of myocardial metabolism.

Do iodinated fatty acids undergo a nonspecific deiodination in the myocardium?

The intracellular and subcellular distribution of 16-(123I)-iodo-9-hexadecenoic acid were studied in isolated rat hearts, perfused with or without glucose. At various time intervals after injection, cardiac lipids were extracted and the activity was determined for all fractions and all lipid classes. The total cardiac activity was maximal within 1 min postinjection and most of the activity was in the aqueous phase. The presence of glucose in the perfusion medium induced an increase of total cardiac and organic fraction activities. In the latter fraction, activity was very low for FFA, but high for triglycerides (TG), and especially polar lipids. The presence of an exogenous substrate, led to a more active esterification of fatty acids. Coronary effluent analysis showed, in the hydrophilic phase, a lower activity spike in the presence than in the absence of glucose. In the mitochondrial fraction most activity occurred in the organic phase, especially as polar lipids. In the nonmitochondrial fraction, activity was much higher in the aqueous phase. At 90 s postinjection of 1-14C-palmitic acid, over 80% of the myocardial activity was found in the hydrophilic fraction, which indicates, as for the iodo-fatty acid (IFA), an immediate and important oxidation, especially without glucose. These data seem to prove that IFA is taken up by the myocardial cell, subsequently enters the mitochondria and, without an early deiodination, is oxidized with iodide release. Changes in IFA metabolism, consecutive to modifications of glucose concentration in the perfusion medium can be observed by external detection of the myocardial activity curve. Omega-Iodinated fatty acids do not undergo a nonspecific deiodination and are therefore well suited for an external study of myocardial metabolism.