Antonella Ricci

Role of reduced expression of SMAD4 in papillary thyroid carcinoma.

It has been demonstrated that transforming growth factor-β (TGFβ) and other members of TGFβ superfamily play an important role in thyroid proliferative diseases. The deficiencies of SMAD4 are responsible to accelerate the malignant progression of neoplastic lesions in several types of tumors. Therefore, the objective of the present study was to determine the functional role of reduced expression of SMAD4 in human papillary thyroid carcinogenesis. For this purpose, we examined the TGFβ response in two cell lines, TPC-1 and BCPAP. Our data demonstrated for the first time that these cells showed a strong reduction in the level of SMAD4 protein, which was responsible for an alteration of TGFβ signaling and for some of the TGFβ-mediated biological effects. The overexpression of SMAD4, restoring TGFβ transduction, determined a significant increase of antiproliferative response to TGFβ, and reduced the invasive behavior of these cells. Therefore, our data indicated that reduction of SMAD4 may play a significant role in thyroid carcinogenesis.

An efficientone-pot access to poly(arylene ethynylene) homopolymers: Use of the Bu3Sn?moiety as a recyclable carrier to introduce the ethynyl unit into the chain

The palladium-catalyzed Stille coupling of an aromatic diiodide with half an equivalent of tributyl(ethynyl)tin results in a complex mixture containing the diethynylaromatic compound, the iodo(ethynyl)aromatic compound, unreacted diiodide and the tributyltin iodide side product. Addition of LDA to this mixture, while leaving the iodoaromatic moieties unaffected, causes deprotonation of the ethynyl functionalities, which immediately recombine with tributyltin iodide to form a mixture of bis(tributylethynyltin)aromatic, iodo(tributylethynyltin)aromatic, and unchanged diiodide. Being the palladium catalyst still active, it is sufficient to warm up this mixture to obtain the coupling of the tributylethynyltin and iodo moieties resulting in the formation of a poly(arylene ethynylene) polymer. Isolation of the polymer is easily and rapidly achieved by precipitation, while distillation of the mother liquor allows recovery of the tributyltin iodide side product. The latter can be utilized for the preparation of new tributyl(ethynyl)tin, thus allowing a convenient turnover of the tributyltin moiety.

The Golgi α-1,6 mannosyltransferase KlOch1p of Kluyveromyces lactis is required for Ca2+/calmodulin-based signaling and for proper mitochondrial functionality

BackgroundProtein N-glycosylation is a relevant metabolic pathway in eukaryotes and plays key roles in cell processes. In yeasts, outer chain branching is initiated in the Golgi apparatus by the alpha-1,6-mannosyltransferase Och1p.ResultsHere we report that, in Kluyveromyces lactis, this glycosyltransferase is also required to maintain functional mitochondria and calcium homeostasis. Cells carrying a mutation in KlOCH1 gene showed altered mitochondrial morphology, increased accumulation of ROS and reduced expression of calcium signalling genes such as calmodulin and calcineurin. Intracellular calcium concentration was also reduced in the mutant cells with respect to the wild type counterparts.Phenotypes that occur in cells lacking the alpha-1,6-mannosyltransferase, including oxidative stress and impaired mitochondria functionality, were suppressed by increased dosage of KlCmd1p. This, in turn, acts through the action of calcineurin.ConclusionsProper functioning of the alpha-1,6-mannosyltransferase in the N-glycosylation pathway of K. lactis is required for maintaining normal calcium homeostasis; this is necessary for physiological mitochondria dynamics and functionality.

A new frontier in the metal-catalyzed cross-coupling reaction field. The palladium-promoted metal–carbon bond formation. Scope and mechanism of a new tool in organometallic synthesis

Abstract The synthetic uses and the investigation of the reaction mechanism of the Pd-catalyzed metal–carbon bond-formation process are accounted. Preparations of simple σ-metal metal acetylides of type M–CC–R (M=Fe, Ru, Mo, W; R=H, Alkyl, Ph), homo and heterobimetallic complexes of type M–CC–Thiop–CC–M′ (Thiop=2,5-thiophene; M, M′=Fe, Ru, Mo, W), polymetallaacetylide tethers of type M–CC–Thiop–CC–M′(η 5 -Cp)–CC–Thiop–CC–(η 5 -Cp)M′–CC–Thiop–CC–M (M=Re, Mn; M′=Fe), and metallaacetylide polymers of type [–M–CC–Ar–CC–] n (Ar=2,5-thiophene, 1,4-phenylene) are reported. By the use of properly designed model substrate principal intermediates (i.e. oxidative addition, transmetalation) involved in the catalytic cycle have been isolated and fully characterized. Kinetic and spectroscopic studies of the reaction mechanism have evidenced that, depending from the reaction conditions, the transmetalation step may proceed by two pathways: (i) in concentrated solutions of the complex of oxidative addition (≅10 −2 M), transmetalation occurs through the formation of the intermediate species which is an associative complex between the substrate and the organostannane (associative mechanism). (ii) When transmetalation is performed using the complex of oxidative addition in lower concentrations (≅10 −4 M), the reaction proceeds through formation of a highly-reactive solvent-coordinate species (dissociative mechanism). These results are showing clear analogies with mechanistic studies of the carbon–carbon coupling process, thus with the use of these model substrates, a unique opportunity to investigate factors affecting the metal–carbon bond formation reaction is offered, as well as the possibility to shed light on unclear aspects of the carbon–carbon coupling itself, a phenomenon of paramount importance in synthetic organic chemistry.

Characterization of Essential Oils Obtained from Abruzzo Autochthonous Plants: Antioxidant and Antimicrobial Activities Assessment for Food Application

In the present study, the essential oils (EOs) of some officinal plants from Abruzzo territory (Italy) were evaluated for their antimicrobial and antioxidant activities and their volatile fraction chemical characterization. The EOs were extracted from Rosmarinus officinalis, Origanum vulgare, Salvia officinalis, Mentha piperita, Allium sativum, Foeniculum vulgare, Satureja montana, Thymus vulgaris and Coriandrum sativum seeds. The antimicrobial activity was screened against thirteen Gram-positive and Gram-negative strains to determine the Minimal Inhibitory Concentration (MIC). The total phenolic content (TPC) and the antioxidant capacity (AOC) were assessed by means of Folin-Ciocâlteu method, and Trolox Equivalent Antioxidant Capacity with 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (TEAC/ABTS), Ferric Reducing Antioxidant Power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays respectively. Among the nine EOs tested, T. vulgaris, S. montana, O. vulgare and C. sativum EOs showed MIC values ranging from 0.625 to 5 μL/mL. The AOC and TPC results for these species were also interesting. The major components for these EOs were thymol for T. vulgaris (44%) and O. vulgare (40%), linalool (77%) for C. sativum, and carvacrol for S. montana (54%). The results allowed the study to establish that these EOs are good candidates for potential application as biopreservatives in foods and/or food manufacture environments.

Design, synthesis and optoelectronic properties of aminoacid derivatives of poly(Arylene ethynylene) platforms: Hybrid bio-synthetic systems for sensoring applications

By means of the modular construction of a large series of poly(arylene ethynylene)s (PAEs) employing Pd-promoted synthetic routes, molecular models of type A-CoC-B-CoC-A and B-CoC-A-CoC-B, and polymers of type [-CoC-A-] n and [-CoC-A-CoC-B-] n carrying a variety of aminoacidic side arms, have been prepared and fully characterized towards their application as sensing materials. The introduction of different aminoacidic groups as side substituents on the conjugated backbone may allow the tuning of the recognition ability of the receptor site towards given analytes. The luminescent sensing properties of these materials towards metal ions were investigated. The flexibility of the synthetic route allows tuning of binding activity, molecular recognition and opto-and electro-properties of the materials, as well as the responses upon exposure to metal ions. All compounds showed high selectivity towards Hg(II) ions, and a signal amplification in Hg(II) detection was observed for the polymeric compound in comparison with small molecule analogues. Further functionalization of aminoacid substituted PAEs with ferrocene moieties allows the electrochemical sensing by change in the oxidation potential of Fe(II)/Fe(III) redox couple, and its dependence with the interaction of aminoacidic side arms with given analytes.