Light Harvesting Unsymmetrical Conjugated Dendrimders as Photosynthetic Mimics

We review the synthesis and photophysical properties of light harvesting phenylacetylene dendrimers with unsymmetrical branching. We describe the steady state and time dependent experiments that are used to characterize energy transfer properties in the conjugated dendrimers. Finally, we describe investigations of the unsymmetrical phenylacetylene dendrimers as potential materials for applications in fluorescence-based sensors, and for non-linear optics.     

Antitumor effects of curcumin and structurally beta-diketone modified analogs on multidrug resistant cancer cells

Using concepts of bioisostery a series of curcumin analogs were synthesized: the diketonic system of the compound was elaborated into enaminones, oximes, and the isoxazole heterocycle. The cell growth inhibitory and apoptosis inducing effects of the new analogs were evaluated by in vitro assays in the hepatocellular carcinoma HA22T/VGH cells, as well as in the MCF-7 breast cancer cell line and in its multidrug resistant (MDR) variant MCF-7R. Increased antitumor activity on all cell lines was found with the isoxazole analog and especially with the benzyl oxime derivative; in the HA22T/VGH cell model, the latter compound inhibited constitutive NF-kappaB activation.     

6-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors

Investigation of a series 6-[2-(4-aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones has led to the discovery of potent 5-HT(1A/1B/1D) receptor antagonists with and without additional SerT affinity. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization.     

Role of Enzyveba in the aerobic bioremediation and detoxification of a soil freshly contaminated by two different diesel fuels

The biodegradability of two commercial diesel fuels, i.e., Diesel and HiQ Diesel, herewith designated as G1 and G2, respectively, spiked to an agricultural soil at 10 g kg⁻¹ was studied under aerobic slurry-phase conditions in the absence and in the presence of Enzyveba, i.e., a characterized commercial source of microorganisms and nutrients. A quite similar hydrocarbon composition was displayed by G1 and G2, which were found to be both extensively and almost completely biodegraded under all conditions after 4.5 months of treatment with a remarkable depletion of initial soil ecotoxicity, in particular in the G2 spiked one. The addition of Enzyveba resulted in a higher availability of cultivable specialized bacteria and fungi in the reactors but this only resulted in a slight intensification of soil bioremediation, probably because of the high contents of nutrients and indigenous specialized microorganisms of the soil. A faster biodegradation of hydrocarbons and a more rapid and extensive depletion of initial ecotoxicity were generally observed in the soil reactors spiked with G2 with respect to those spiked with G1 probably for the G2 content of additives capable of improving hydrocarbons bioavailability.     

Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release

Airway smooth muscle (ASM) from infant guinea pigs has less spontaneous relaxation during stimulation than ASM from adults. Inhibition of cyclooxygenase (COX), which catalyzes the production of prostanoids, increases this relaxation in infant ASM and abolishes age differences, thus suggesting that prostanoids reduce relaxation in infant ASM. In this study, we investigated whether leukotrienes are also involved in reducing spontaneous relaxation; whether the two COX isoforms, COX-1 and COX-2, differentially regulate spontaneous relaxation; and whether prostanoid release is developmentally regulated in guinea pig ASM. In different age groups, we measured relaxation during and after electrical stimulation in tracheal strips as well as prostanoid release from tracheal segments. Relaxation was studied in the absence and in the presence of a lipoxygenase inhibitor, a cysteinyl leukotriene receptor-1 antagonist, a COX-1 inhibitor, or a COX-2 inhibitor. We found that inhibition of lipoxygenase or cysteinyl leukotriene receptor-1 antagonism did not increase spontaneous relaxation at any age, thus excluding a role for leukotrienes in this phenomenon. Inhibition of COX-2, but not COX-1, promoted spontaneous relaxation. The basal release of prostanoids was more abundant in tissue from infant animals and decreased significantly with age. Thromboxane B2 was the most abundant metabolite released at all ages. Electrical stimulation and epithelium removal did not affect the age difference in prostanoid release. We conclude that increased basal prostanoid release contributes to the reduced spontaneous relaxation in immature guinea pig ASM compared with older animals. By regulating ASM relaxation, prostanoids may play a role in the airway hyperresponsiveness at a young age.     

Arabidopsis 10-formyl tetrahydrofolate deformylases are essential for photorespiration

In prokaryotes, PurU (10-formyl tetrahydrofolate [THF] deformylase) metabolizes 10-formyl THF to formate and THF for purine and Gly biosyntheses. The Arabidopsis thaliana genome contains two putative purU genes, At4g17360 and At5g47435. Knocking out these genes simultaneously results in plants that are smaller and paler than the wild type. These double knockout (dKO) mutant plants show a 70-fold increase in Gly levels and accumulate elevated levels of 5- and 10-formyl THF. Embryo development in dKO mutants arrests between heart and early bent cotyledon stages. Mature seeds are shriveled, accumulate low amounts of lipids, and fail to germinate. However, the dKO mutant is only conditionally lethal and is rescued by growth under nonphotorespiratory conditions. In addition, culturing dKO siliques in the presence of sucrose restores normal embryo development and seed viability, suggesting that the seed and embryo development phenotypes are a result of a maternal effect. Our findings are consistent with the involvement of At4g17360 and At5g47435 proteins in photorespiration, which is to prevent excessive accumulation of 5-formyl THF, a potent inhibitor of the Gly decarboxylase/Ser hydroxymethyltransferase complex. Supporting this role, deletion of the At2g38660 gene that encodes the bifunctional 5,10-methylene THF dehydrogenase/5,10-methenyl THF cyclohydrolase that acts upstream of 5-formyl THF formation restored the wild-type phenotype in dKO plants.     

Nerve injury signaling

Although neurons within the peripheral nervous system (PNS) have a remarkable ability to repair themselves after injury, neurons within the central nervous system (CNS) do not spontaneously regenerate. This problem has remained recalcitrant despite a century of research on the reaction of axons to injury. The balance between inhibitory cues present in the environment and the intrinsic growth capacity of the injured neuron determines the extent of axonal regeneration following injury. The cell body of an injured neuron must receive accurate and timely information about the site and extent of axonal damage in order to increase its intrinsic growth capacity and successfully regenerate. One of the mechanisms contributing to this process is retrograde transport of injury signals. For example, molecules activated at the injury site convey information to the cell body leading to the expression of regeneration-associated genes and increased growth capacity of the neuron. Here we discuss recent studies that have begun to dissect the injury-signaling pathways involved in stimulating the intrinsic growth capacity of injured neurons.     

Environmentally relevant cadmium concentrations affect development and induce apoptosis of <Emphasis Type="Italic">Paracentrotus lividus</Emphasis> larvae cultured in vitro

Sea urchin embryos and larvae represent suitable model systems on where to investigate the effects of heavy metals on development and cell viability. Here, we tested the toxic effects of low (10⁻¹² M), medium (10⁻⁹ M), and high (10⁻⁶ M) cadmium chloride concentrations, mimicking unpolluted, moderately and highly polluted seawaters, respectively, on Paracentrotus lividus sea urchins offspring. Larvae were continuously treated from fertilization and inspected at time intervals comprised between 10 and 30 days of development. Delays and/or morphological abnormalities were firstly evident in larvae treated for 15 days with high cadmium (10⁻⁶ M) and for 25 days with medium cadmium (10⁻⁹ M). Major defects consisted in the reduction and lack of arms and skeleton elongation. No obvious differences with respect to controls were observed in embryos/larvae exposed to low cadmium (10⁻¹² M), even after 30 days of exposure. Using in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL) assay on larvae whole mounts, we detected apoptosis after 10 days of treatment with 10⁻⁶ and 10⁻⁹ M CdCl_2, when no morphological abnormalities were recognizable yet. Supernumerary apoptotic cells were found in arm buds, ciliary bands, and apex. In conclusion, echinoderm embryos and larvae represent candidates of choice for the study of stress and defense mechanisms activated by cadmium exposure.     

Anatomical evidence for ileal Peyer’s patches innervation by enteric nervous system: a potential route for prion neuroinvasion?

We have examined the innervation of the gut-associated lymphoid system of the sheep ileum, with a view to identifying potential sites for neuroinvasion by pathogens, such as prions (PrP^Sc). Special attention has been paid to the follicles of Peyer’s patches (PPs), which are major sites of PrP^Sc accumulation during infection. Evidence exists that the enteric nervous system, together with the parasympathetic and sympathetic pathways projecting to the intestine, are important for PrP^Sc entry into the central nervous system. Thus, PrP^Sc might move from PPs to the neurons and nerve fibres that innervate them. We investigated, by immunohistochemistry and retrograde tracing (DiI) from the follicles, the distribution and phenotype of enteric neurons innervating the follicles. Antibodies against protein gene product 9.5, tyrosine hydroxylase, dopamine β hydroxylase, choline acetyltransferase, calbindin (CALB), calcitonin gene-related peptide (CGRP), and nitric oxide synthase were used to characterise the neurons. Immunoreactivity for each of these was observed in fibres around and inside PP follicles. CGRP-immunoreactive fibres were mainly seen at the follicular dome. Retrograde tracing revealed submucosal neurons that contributed to the innervation of PPs, including Dogiel type II neurons and neurons immunoreactive for CALB and CGRP. The major source of the adrenergic fibres are the sympathetic ganglia. Our results thus suggest that enteric and sympathetic neurons are involved during the first stage of neuroinvasion, with neurons connecting to them acting as potential carriers of PrP^Sc to the central nervous system. This study was supported by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR, PRIN 2006), from the Fondazione del Monte di Bologna e Ravenna and from the National Health and Medical Research Council of Australia (grant no. 400020).