Homing Behaviour in Polyergus rufescens Latr. (Hymenoptera,Formicidae)

Homing mechanisms of the European slave-making ant Polyergus rufescens Latr. are investigated by field experiments. The analysis of the behaviour and paths of both homing scouts and raiders after passive displacement showed that: i. Scouts probably home by using a path integration system based on celestial cues; and ii. Displaced raiders do not seem to adopt such a vectorial orientation mechanism. Moreover, we found that passively displaced scouts exhibit a systematic search strategy for the nest after a rectilinear path. By contrast, raiders perform a similar search pattern just after release. Similarities between Cataglyphis and Polyergus homing behaviour are discussed.     

Small Molecule Deubiquitinase Inhibitors Promote Macrophage Anti-Infective Capacity

The global spread of anti-microbial resistance requires urgent attention, and diverse alternative strategies have been suggested to address this public health concern. Host-directed immunomodulatory therapies represent one approach that could reduce selection for resistant bacterial strains. Recently, the small molecule deubiquitinase inhibitor WP1130 was reported as a potential anti-infective drug against important human food-borne pathogens, notably Listeria monocytogenes and noroviruses. Utilization of WP1130 itself is limited due to poor solubility, but given the potential of this new compound, we initiated an iterative rational design approach to synthesize new derivatives with increased solubility that retained anti-infective activity. Here, we test a small library of novel synthetic molecules based on the structure of the parent compound, WP1130, for anti-infective activity in vitro. Our studies identify a promising candidate, compound 9, which reduced intracellular growth of L. monocytogenes at concentrations that caused minimal cellular toxicity. Compound 9 itself had no bactericidal activity and only modestly slowed Listeria growth rate in liquid broth culture, suggesting that this drug acts as an anti-infective compound by modulating host-cell function. Moreover, this new compound also showed anti-infective activity against murine norovirus (MNV-1) and human norovirus, using the Norwalk virus replicon system. This small molecule inhibitor may provide a chemical platform for further development of therapeutic deubiquitinase inhibitors with broad-spectrum anti-infective activity.     

alpha-Lipoic acid modulates extracellular matrix and angiogenesis gene expression in non-healing wounds treated with hyperbaric oxygen therapy

alpha-Lipoic acid (LA) has been found previously to accelerate wound repair in patients affected by chronic wounds who underwent hyperbaric oxygen (HBO) therapy. Because proteinases are important in wound repair, we hypothesized that LA may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Patients undergoing HBO therapy were double-blind randomized into two groups: the LA group and the placebo group. Gene expression profiles for MMPs and for angiogenesis mediators were evaluated in biopsies collected at the first HBO session, at the seventh HBO session, and after 14 days of HBO treatment. ELISA tests were used to validate microarray expression of selected genes. LA supplementation in combination with HBO therapy downregulated the inflammatory cytokines and the growth factors which, in turn, affect MMPs expression. The disruption of the positive autocrine feedback loops that maintain the chronic wound state promotes progression of the healing process.     

The migratory insertion of carbon monoxide in pentamethylcyclopentadienyliridium (III) complexes. Structural effects on reactivity and mechanism for rhodium and iridium systems

The reactions of complex (C₅Me₅)Ir(Cl) (CO) (Me) (1a) with cyclohexylisocyanide and phosphines (L=CyNC, PHPh₂, PMePh₂, PMe₂Ph) give the products of alkyl migratory insertion (C₅Me₅Ir(Cl) (COMe) (L), in toluence or tetrahydrofuran at 323 K or higher temperature. The phenyl analogue (C₅Me₅)Ir(Cl)(CO)(Ph) or the iodide complexes (C₅Me₅)Ir(I) (CO) (R) (R=Me, Ph_are not reactive under the same conditions. The reaction of (C₅Me₅)Ir(Cl)(CO)(Me) with PMePh₂ and PMe₂Ph in acetonitrile yields the chloride substitution product [(C₅Me₅)Ir(CO)(L)(Me)]⁺Cl⁻. Kinetic measurements for the reactions of (C₅Me₅)Ir(Cl)(CO)(Me) in toluene are first order in the iridium complex and exhibit a saturation dependence on the incoming donors L. Analysis of the data suggests a two-step process involving (i) rapid formation of a molecular complex [(C₅Me₅)Ir(Cl)(CO)(Me), (L)], in which the structure of 1a is unperturbed within the limits of spectroscopic analysis, and (ii) rate determining methyl migration. The reaction parameters are K for the pre-equilibrium step (K = 1.5 (CyNC), 7.3 (PHPh₂), 7.1 (PMePh₂) dm³ mol⁻¹ at 323 K) and k₂ for the slow carbon---carbon bond formation (k₂ (10⁵) = 6.9 (CyNC), 1.2 (PHPh₂), 1.0 (PMePh₂) s⁻¹ at 323 K). The activation parameters for the methyl migration step in the reaction with PMePh₂ obtained between 308 and 338 K, are ΔH^≠ = 106±16 kJ mol⁻¹ and ΔS^≠ = − 14±5 J K⁻¹ mol⁻¹. The reaction of 1a with PMePh₂ proceeds at similar rates in tetrahydrofuran (K = 3.7 dm³ mol⁻¹, k₂ (10⁵) = 1.2 s⁻¹, 323 K). The crystal structure of (C₅Me₅)Ir(Cl)(COMe) (PMe₂Ph) has been determined by X-ray diffraction. C₂₀H₂₉ClOPIr: M_r = 544.1, monoclinic, P2₁/n, A = 8.084 (2), B = 9.030(2), C = 28.715 (3) Å, β = 91.41 (3)°, Z = 4, D_c = 1.71 g cm⁻³, V = 2095.5 ų, room temperatyre, Mo K, γ = 0.71069, μ = 65.55 cm⁻¹, F(000) = 1044, R = 0.037 for 2453 independent observed reflections. The complex shows a deformed tetrahedral coordination assuming the η⁵-C₅Me₅ molecular fragment as a single coordination site. The iridium-chlorine bond is staggered with respect to two adjacent C(ring)-methyl bonds, while the Ir---P and the Ir---COMe bonds are eclipsed with respect to C(ring)-methyl bonds.     

CH(3)ReO(3)-catalyzed oxidation of cholesta-5,7-dien-3beta-yl acetate with the urea-hydrogen peroxide adduct under various conditions. Synthesis of the natural epoxy sterol 9alpha,11alpha-epoxy-5alpha-cholest-7-en-3beta,5,6beta-triol

This article describes the oxidation of cholesta-5,7-dien-3beta-yl acetate (4) with the urea-hydrogen peroxide adduct (UHP) using methyltrioxorhenium (MTO) as catalyst, under various conditions. Specifically, the effects of using different solvents (CHCl(3) and ethers) and additives (EtOH and pyridine) on the course of the MTO-catalyzed oxidation of 4 were investigated. Some new steroids (6, 9, 10 and 11), obtained from this oxidation, were isolated and characterized on the basis of chemical evidence and interpretation of spectroscopic data including H-H COSY and HMBC experiments. The optimal solvent for the oxidation of 4 with MTO/UHP oxidizing system was diethyl ether. In this solvent the reaction is clean and gave as the main product 5,6beta-dihydroxy-5alpha-cholest-7-en-3beta-yl acetate (8, 65% yield), obtained with a more simple procedure and with a higher yield than that reported in literature. Sterol 8 is a key intermediate compound in the synthesis of many steroids of marine origin, biologically active, oxygenated at the B/C rings. In fact, starting from diol 8, we performed the synthesis of the natural cytotoxic epoxy sterol 9alpha,11alpha-epoxy-5alpha-cholest-7-en-3beta,5,6beta-triol (15, 21% yield) with an improvement in yield and number of steps over a synthesis of the same natural product previously reported. When the oxidation of 4 with the MTO/UHP system in diethyl ether was performed in the presence of pyridine as ligand, the unsaturated epoxide 5,6alpha-epoxy-5alpha-cholest-7-en-3beta-yl acetate (10, 90% yield) was obtained after only 5 min in good yield. In fact, pyridine, besides having beneficial effect on the reaction rate, shuts down the ring opening reactions, as reported in literature.     

Activation of Brain Indoleamine-2,3-dioxygenase Contributes to Depressive-Like Behavior Induced by an Intracerebroventricular Injection of Streptozotocin in Mice

Neurochemical Research - There is a lack of information concerning the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in...     

Human immunodeficiency virus type 1 gp120 induces abnormal maturation and functional alterations of dendritic cells: a novel mechanism for AIDS pathogenesis

Dendritic cells (DCs) play a crucial role in bridging innate and acquired immune responses to pathogens. In human immunodeficiency virus type 1 (HIV-1) infection, immature DCs (iDCs) are also main targets for HIV-1 at the mucosal level. In this study, we evaluated the effects of HIV-1-DC interactions on the maturation and functional activity of these cells. Exposure of human monocyte-derived iDCs to either aldrithiol-2-inactivated HIV-1 or gp120 led to an upmodulation of activation markers indicative of functional maturation. Despite their phenotype, these cells retained antigen uptake capacity and showed an impaired ability to secrete cytokines or chemokines and to induce T-cell proliferation. Although gp120 did not interfere with DC differentiation, the capacity of these cells to produce interleukin-12 (IL-12) upon maturation was markedly reduced. Likewise, iDCs stimulated by classical maturation factors in the presence of gp120 lacked allostimulatory capacity and did not produce IL-12, in spite of their phenotype typical of activated DCs. Exogenous addition of IL-12 restores the allostimulatory capacity of gp120-exposed DCs. The finding that gp120 induces abnormal maturation of DCs linked to profound suppression of their activities unravels a novel mechanism by which HIV can lead to immune dysfunction in AIDS patients.     

Bromoform,mycosporine-like amino acids and phycobiliprotein content and stability in Asparagopsis armata during long-term indoor cultivation

Journal of Applied Phycology - As the commercial use of seaweed for natural product extraction calls for abundant, uniform biomass, this study focused on the production and the variability of the...     

The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein.

alpha-Synuclein-containing aggregates represent a feature of a variety of neurodegenerative disorders, including Parkinson's disease (PD). However, mechanisms that promote intraneuronal alpha-synuclein assembly remain poorly understood. Because pesticides, particularly the herbicide paraquat, have been suggested to play a role as PD risk factors, the hypothesis that interactions between alpha-synuclein and these environmental agents may contribute to aggregate formation was tested in this study. Paraquat markedly accelerated the in vitro rate of alpha-synuclein fibril formation in a dose-dependent fashion. When mice were exposed to the herbicide, brain levels of alpha-synuclein were significantly increased. This up-regulation followed a consistent pattern, with higher alpha-synuclein at 2 days after each of three weekly paraquat injections and with protein levels returning to control values by day 7 post-treatment. Paraquat exposure was also accompanied by aggregate formation. Thioflavine S-positive structures accumulated within neurons of the substantia nigra pars compacta, and dual labeling and confocal imaging confirmed that these aggregates contained alpha-synuclein. The results suggest that up-regulation of alpha-synuclein as a consequence of toxicant insult and direct interactions between the protein and environmental agents are potential mechanisms leading to alpha-synuclein pathology in neurodegenerative disorders.     

Co-cultures of hepatocytes with epithelial-like cell lines: Expression of drug-biotransformation activities by hepatocytes

To improve long-term expression of drug biotransformation activities in hepatocytes, we have examined the suitability of several epithelial-like cell lines (MDCK, MS and L-132) for supporting functional co-cultures with rat hepatocytes. Cells were selected on the basis of their compatibility with hepatocytes, formation of stable monolayers in the absence of serum and lack of drug biotransformation activities. The expression of individual elements of the biotransformation system was evaluated in these co-cultures. Co-cultured hepatocytes remained viable and showed a characteristic polygonal shape for more than a week. Depending on the cell line used, levels of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activities of co-cultured hepatocytes oscillated between 24–47% of their initial value after 4 days in culture. The highest levels of monooxygenase activity were found in hepatocytes co-cultured with MS cells (41–47%). In contrast, these activities decreased to 6% when hepatocytes were maintained in pure culture for the same period. The activities of the conjugating enzymes UDP-glucuronyltransferase and glutathione S-transferase were maintained at nearly the initial levels during the complete period of study, both in pure and mixed-cultures, regardless of the cell line used. MS cells adapted themselves much better to serum-free culture conditions, and the co-culture with rat hepatocyte was technically easier. After one week, total cytochrome P450 and reduced glutathione in rat hepatocytes/MS co-cultures were 31% and 127% respectively of the day O values, whereas they were undetectable in pure culture. A clear induction of monooxygenase activities by methylcholanthrene, phenobarbital and ethanol could be observed by the 5th day in MS cells/hepatocyte co-cultures. The fact that the results of our work show the suitability of MS cells, an epithelial-derived cell line, for improving the expression of biotransformation enzymes of cultured hepatocytes opens new possibilities of simplifying co-cultures for their use in drug-metabolism studies.Abbreviations AHH aryl hydrocarbon hydroxylase - CDNB 1-chloro-2,4-dinitrobenzene - DMEM Dulbecco's modified Eagle's medium - ECOD 7-ethoxycoumarin O-deethylase - EDTA ethylenediamine tetraacetic acid - Et-OH ethanol - GSH reduced glutathione - GSH-t glutathione S-transferase - MC 3-methylcholanthrene - PB phenobarbital - UDP-Gt UDP-glucuronyltransferase