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In this work, the ability of several bis-viologen axles to thread a series of heteroditopic tris(N-phenylureido)calix[6]arene wheels to give interwoven supramolecular complexes to the [3]pseudorotaxane type was studied. The unidirectionality of the threading process inside these nonsymmetric wheels allows the formation of highly preorganised [3]pseudorotaxane and [3]rotaxane species in which the macrocycles phenylureido moieties, functionalised with either ester, carboxylic, or hydroxymethyl groups, are facing each other. As verified by NMR and semiempirical computational studies, these latter compounds possess the correct spatial arrangement of their subcomponents, which could lead, in principle, upon proper bridging reaction, to the realisation of upper-to-upper molecular capsules that are based on calix[6]arene derivatives. [ABSTRACT FROM AUTHOR]

Tris-( N-phenylureido)-calix[6]arene derivatives are heteroditopic non-symmetric molecular hosts that can form pseudorotaxane complexes with 4,4′-bipyridinium-type guests. Owing to the unique structural features and recognition properties of the calix[6]arene wheel, these systems are of interest for the design and synthesis of novel molecular devices and machines. We envisaged that the incorporation of photoactive units in the calixarene skeleton could lead to the development of systems the working modes of which can be governed and monitored by means of light-activated processes. Here, we report on the synthesis, structural characterization, and spectroscopic, photophysical, and electrochemical investigation of two calix[6]arene wheels decorated with three naphthyl groups anchored to either the upper or lower rim of the phenylureido calixarene platform. We found that the naphthyl units interact mutually and with the calixarene skeleton in a different fashion in the two compounds, which thus exhibit a markedly distinct photophysical behavior. For both hosts, the inclusion of a 4,4 ′-bipyridinium guest activates energy- and/or electron-transfer processes that lead to non-trivial luminescence changes. [ABSTRACT FROM AUTHOR]

A series of calix[4]arene semitubes (4a–c) having alkyl bridging spacers of different lengths and flexibilities on their lower rim was synthesised and characterised in solution and in the solid state by 1H NMR spectroscopy and X-ray crystallography. The binding properties of these novel ditopic hosts toward a series of N-alkylpyridinium ion pairs were investigated in low polar media by 1H NMR and UV-vis spectroscopy and compared with those of the corresponding calix[4]arene monotopic host 5. These studies showed that in low polar solvents, the calix[4]arene semitubes behave as homoditopic hosts giving rise with N-alkylpyridinium ion pairs to supramolecular adducts of 1 : 2 host–guest stoichiometry. [ABSTRACT FROM AUTHOR]

Tris-(N-phenylureido)-calix[6]arenes are heteroditopic non-symmetric molecular wheels that, in apolar media, bind viologen-based molecular axles in a pseudorotaxane-type fashion. Because of the precise kinetic requirements associated with the threading process, in apolar solvents, the dicationic portion of the axle enters the calixarene annulus exclusively from the upper rim. With the general aim to develop new prototypes of molecular devices and machines whose functions could be governed through a wider set of control elements, we envisaged that the unique properties of these calixarene wheels could be transferred to the synthesis of new catenanes for the construction of unidirectional rotary motors. Herein, we describe the synthesis of a tris(N-phenylureido)calix[6]arene-based catenane by applying the intramolecular ring-closing metathesis reaction for the catenation step on a pre-formed pseudorotaxane. [ABSTRACT FROM AUTHOR]

Oriented rotaxanes composed of tris( N-phenylureido)calix[6]arene wheel 1 and N, N′-dialkyl viologen-based axles were synthesized in which the span between the diphenylacetyl stoppers at the wheel upper and lower rim and the bis-pyridinium cation portion of the axial component is different in length. A sequential synthetic pathway was followed to achieve the selective formation of orientational isomers, wherein the short (or long) chain of the axle is positioned either on the upper or lower rim of the wheel. The synthetic strategy adopted involves the upper rim threading of axles 2a- c to yield oriented pseudorotaxanes, which were then stoppered in situ. The structure of the oriented rotaxanes was unravelled by detailed NMR experiments, and their spectroscopic, electrochemical and dynamic properties were investigated by UV/Vis, cyclic voltammetry, and EPR measurements. The results were compared with those of their symmetric counterparts. [ABSTRACT FROM AUTHOR]

We describe the active template effect of a calix[6]arene host towards the alkylation of a complexed pyridylpyridinium guest. The acceleration of the reaction within the cavity is significant and rim-selective, enabling the efficient preparation of rotaxanes with full control of the mutual orientation of their nonsymmetric components. [ABSTRACT FROM AUTHOR]

The article discusses topics related to the particulars of Intercultural Communication and Leadership School (ICLS) in Rome, Italy. It mentions the purpose of ICLS, which is to promote the better future by helping young leaders on their way through provision of extra tools. It also mentions that ICLS tries to contribute to the reduction and resolving of tension and conflict between communities, both local and international. The article also discusses various topics related to ICLS including cultural leadership, principles of ICLS, and principles in practices.

Background: Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Methods: Urinary levels of col(IV)α1, col(IV)α3 and col(IV)α5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)α chains, from col(IV)α1 to col(IV)α5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Results: Urinary levels of col(IV)α1, col(IV)α3, col(IV)α5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)α1 and col(IV)α3 urinary excretion correlated with the degree of chronic histological damage [col(IV)α1 R = 0.44, p < 0.001; col(IV)α3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)α5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)α3, col(IV)α4 and col(IV)α5 chains [p < 0.01 for all]. Conclusion: Patients with chronic acquired glomerulopathies show important alterations in the col(IV)α chain network mimicking some molecular features of the X-linked Alport’s syndrome. Further studies are needed to show whether urinary levels of the col(IV)α chains may be used as markers for monitoring renal injury. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Calcein-acetoxymethylester (calcein-AM) is a non-fluorescent, cell permeant compound, which is converted by intracellular esterases into calcein, an anionic fluorescent form. It is used in microscopy and fluorometry and provides both morphological and functional in- formation of viable cells. In this study we have tested the response of calcein-AM to oxidation. In cell-free fluorometric assays, H2O2 and xanthine-xanthine oxidase induced a dose-dependent emission of the AM form but had no effects on calcein. Fluorometric and confocal microscopy tests on human fibroblasts confirmed that the cell permeant AM form is the actual sensor since its removal from culture medium, and its consequent back-diffusion, made the system insensitive to oxidative stimuli. In time- lapse confocal microscopy, calcein-AM detected changes in the intracellular redox state following direct oxidation (H2O2, xanthine-xanthine oxidase) and phorbol ester treatment. Comparative tests showed that calcein-AM sensitivity to oxidation is about one order of magnitude higher than other fluorescein derivatives. The absence of leakage, due to the presence of the probe in the extracellular compartment, and its low toxicity allow to perform experiments for prolonged times following the response to the same or different stimuli repeatedly applied. We propose calcein-AM as a sensitive tool for intracellular ROS generation in living cells with useful applications for real-time imaging in confocal microscopy. [ABSTRACT FROM AUTHOR]

Background: Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated., Methods: Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls., Results: Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all]., Conclusion: Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury., (Copyright 2007 S. Karger AG, Basel.)

The resistance to L-asparaginase (ASNase) has been associated to the overexpression of asparagine synthetase (AS), although the role played by other metabolic adaptations has not been yet defined. Both in ASNase-sensitive Jensen rat sarcoma cells and in ARJ cells, their ASNase-resistant counterparts endowed with a five-fold increased AS activity, ASNase treatment rapidly depletes intracellular asparagine. Under these conditions, cell glutamine is also severely reduced and the activity of glutamine synthetase (GS) is very low. After 24 h of treatment, while sensitive cells have undergone massive apoptosis, ARJ cells exhibit a marked increase in GS activity, associated with overexpression of GS protein but not of GS mRNA, and a partial restoration of glutamine and asparagine. However, when ARJ cells are treated with both ASNase and L-methionine-sulfoximine (MSO), an inhibitor of GS, no restoration of cell amino acids occurs and the cell population undergoes a typical apoptosis. No toxicity is observed upon MSO treatment in the absence of ASNase. The effects of MSO are not referable to depletion of cell glutathione or inhibition of AS. These findings indicate that, in the presence of ASNase, the inhibition of GS triggers apoptosis. GS may thus constitute a target for the suppression of ASNase-resistant phenotypes., (Copyright (c) 2005 S. Karger AG, Basel.)

Mouse oocytes at the germinal vesicle stage are characterized by one of two nuclear morphologies: surrounded nucleolus (SN), in which the nucleolus is surrounded by a rim of Hoechst positive chromatin and not surrounded nucleolus (NSN), in which this rim is essentially absent. This morphological difference has a biological relevance as NSN oocytes are transcriptionally active, yet incapable of development beyond the two-cell stage. Whereas SN oocytes, which are transcriptionally inactive, are capable of development to the blastocyst stage. To further our understanding of the nuclear organization of the mouse oocyte during folliculogenesis, we have conducted a series of investigations employing silver methods that stain nucleolus organizer region (NOR), centromeres, and heterochromatin, as well as, specific antibodies for centromeres. Results obtained by a variety of microscopic methods (light, electron, immunochemical, and confocal) demonstrate: (1) a changing pattern of NOR staining during folliculogenesis that is specific to follicular type, and (2) significant differences in the organization of NORs and centromeres of isolated, antral NSN, and SN oocytes. These observations suggest possible means by which, chromosomes of mature, germinal vesicle oocytes are organized with respect to the nucleolus., (Copyright 2003 Wiley-Liss, Inc.)

Organic mercury is a well-known neurotoxicant although its mechanism of action has not been fully clarified. In addition to a direct effect on neurons, much experimental evidence supports an involvement of the glial component. We assessed methylmercury hydroxide (MeHgOH) toxicity in a glial model, C6 glioma cells, exposed in the 10(-5)-10(-8) M range. The time course of the effects was studied by time-lapse confocal microscopy and supplemented with biochemical data. We have monitored cell viability and proliferation rate, reactive oxygen species (ROS), mitochondrial transmembrane potential, DNA oxidation, energetic metabolism and modalities of cell death. The earliest effect was a measurable ROS generation followed by oxidative DNA damage paralleled by a partial mitochondrial depolarization. The effect on cell viability was dose dependent. TUNEL, caspase activity and real-time morphological observation of calcein-loaded cells showed that apoptosis was the only detectable mode of cell death within this concentration range. N-acetyl-cysteine (NAC) or reduced glutathione (GSH) completely prevent the apoptotic effect of MeHgOH. The lowest effective MeHgOH concentration was 10(-7) M for ROS and DNA OH-adducts generation. The effect of submicromolar concentrations of MeHgOH on C6 cells could be relevant in the developmental neurotoxicity caused by low dose, long-term exposures, such as those of food origin. In addition, we have shown that the same concentrations are effective in the induction of DNA oxidative damage, with further potential pathogenetic implications., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To evaluate the apoptotic effect of the chemokine growth-related oncogene alpha (GROalpha), which we recently reported to be up-regulated in osteoarthritis (OA) chondrocytes. Chondrocyte apoptosis is considered to be a major determinant of cartilage damage in OA, a disease resulting from the aberrant production of inflammatory mediators (cytokines and chemokines) and effectors (matrix metalloproteinases and reactive oxygen and nitrogen species) by chondrocytes., Methods: We investigated the apoptotic effect of GROalpha on isolated human cells and on in vitro-cultured cartilage explants by conventional methods (morphology, detection of DNA fragmentation in situ and in solution, exposure of phosphatidylserine) and by analysis of "early" biochemical events (plasma membrane depolarization, activation of caspase 3, and phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase)., Results: We clearly demonstrated that GROalpha was able to initiate a series of morphologic, biochemical, and molecular changes that led to chondrocyte apoptosis. Moreover, we found that additional signals delivered from the extracellular matrix (ECM) were essential in the control of chondrocyte susceptibility to GROalpha-induced apoptosis, since cell death was detected only when cells were stimulated after reestablishment of their proper interactions with the ECM, or in cartilage explant samples with reduced ECM, as indicated by decreased Safranin O staining., Conclusion: GROalpha can induce apoptosis in articular chondrocytes, and the induction is dependent upon additional signals from the ECM. These findings are relevant to understanding the pathogenesis of OA, in view of the availability of the GROalpha chemokine in the joint space in the course of this rheumatic disease.