A stereodynamic fluorescent probe for amino acids. Circular dichroism and circularly polarized luminescence analysis

The use of stereodynamic probes is becoming one of the leading strategies for the fast and effective determination of enantiomeric excess. Recently, we reported a series of novel molecular architectures based on a modified tris(2‐pyridylmethyl)amine complex (TPMA), which are able to amplify the electronic CD, in the case of Zn(II) assemblies and vibrational CD, in the case of Co(II) assemblies. Herein, we report a structural modification of the ligand with the purpose to obtain a fluorescent chiral probe. The study deals with the synthesis of the novel ligand, the formation of the self‐assembly system with amino acids, and the study of the electronic CD and circularly polarized luminescence.     

Enantiopure Ti(IV) amino triphenolate complexes as NMR chiral solvating agents

Enantiopure Ti(IV) complexes bearing pseudo-C(3) amino triphenolate ligands have been synthesized and characterized. The complexes bearing ortho phenyl groups act as (1)H NMR chiral solvating agent (CSA) for the stereochemical analysis of a series of sulfoxides. The coordination of a Lewis base coligand (sulfoxide) and the presence of aromatic rings are the key structural factors for the efficiency of the CSA.     

High‐ and low‐frequency mechanical properties of living starfish oocytes

We studied the mechanical properties of living starfish oocytes belonging to two species, Astropecten Auranciacus and Asterina pectinifera, over a wide range of timescales. We monitored the Brownian motion of microspheres injected in the cytoplasm using laser particle‐tracking (LPT) and video multiple‐particle‐tracking (MPT) techniques, to explore high‐ and low‐frequency response ranges, respectively. The analysis of the mean‐square‐displacements (MSD) allowed us to characterize the samples on different timescales. The MSD behavior is explained by three power‐law exponents: for short times (τ < 1 ms) it reflects the semiflexible behavior of the actin network; for intermediate timescales (1 ms < τ < 1 s) it is similar to that of a soft‐glass material; finally for long times (τ > 1 s) it behaves mainly like a viscous medium. We computed and compared the viscoelastic moduli using a recently proposed model describing the frequency response of the cell material. The large fluctuations found in the MSD over hundreds of trajectories indicate and confirm the significant cytoplasm heterogeneity. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Fibroblast Growth Factor Receptor-2 Expression in Thyroid Tumor Progression: Potential Diagnostic Application

Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis.     

San Bernardino Cave (Italy) and the Appearance of Levallois Technology in Europe: Results of a Radiometric and Technological Reassessment

The introduction of Levallois technology in Europe marked the transition from the Lower to the early Middle Paleolithic. This new method of flake production was accompanied by significant behavioral changes in hominin populations. The emergence of this technological advance is considered homogeneous in the European archaeological record at the Marine isotopic stage (MIS) 9/MIS 8 boundary. In this paper we report a series of combined electron spin resonance/U-series dates on mammal bones and teeth recovered from the lower units of San Bernardino Cave (Italy) and the technological analyses of the lithic assemblages. The San Bernardino Cave has yielded the earliest evidence of Levallois production on the Italian Peninsula recovered to date. In addition to our results and the review of the archaeological record, we describe the chronological and geographical differences between European territories and diversities in terms of technological developments. The belated emergence of Levallois technology in Italy compared to western Europe corresponds to the late Italian Neanderthal speciation event. The new radiometric dates and the technological analyses of San Bernardino Cave raise the issue of the different roles of glacial refugia in the peopling and the spread of innovative flaking strategies in Europe during the late Middle Pleistocene.     

Exendin-4 Induces Cell Adhesion and Differentiation and Counteracts the Invasive Potential of Human Neuroblastoma Cells

Exendin-4 is a molecule currently used, in its synthetic form exenatide, for the treatment of type 2 diabetes mellitus. Exendin-4 binds and activates the Glucagon-Like Peptide-1 Receptor (GLP-1R), thus inducing insulin release. More recently, additional biological properties have been associated to molecules that belong to the GLP-1 family. For instance, Peptide YY and Vasoactive Intestinal Peptide have been found to affect cell adhesion and migration and our previous data have shown a considerable actin cytoskeleton rearrangement after exendin-4 treatment. However, no data are currently available on the effects of exendin-4 on tumor cell motility. The aim of this study was to investigate the effects of this molecule on cell adhesion, differentiation and migration in two neuroblastoma cell lines, SH-SY5Y and SK-N-AS. We first demonstrated, by Extra Cellular Matrix cell adhesion arrays, that exendin-4 increased cell adhesion, in particular on a vitronectin substrate. Subsequently, we found that this molecule induced a more differentiated phenotype, as assessed by i) the evaluation of neurite-like protrusions in 3D cell cultures, ii) the analysis of the expression of neuronal markers and iii) electrophysiological studies. Furthermore, we demonstrated that exendin-4 reduced cell migration and counteracted anchorage-independent growth in neuroblastoma cells. Overall, these data indicate for the first time that exendin-4 may have anti-tumoral properties.     

Liver X Receptor (LXR) activation negatively regulates visfatin expression in macrophages

Adipose tissue macrophages (ATM) are the major source of visfatin, a visceral fat adipokine upregulated during obesity. Also known to play a role in B cell differentiation (pre-B cell colony-enhancing factor (PBEF)) and NAD biosynthesis (nicotinamide phosphoribosyl transferase (NAMPT)), visfatin has been suggested to play a role in inflammation.Liver X Receptor (LXR) and Peroxisome Proliferator-Activated Receptor (PPAR)γ are nuclear receptors expressed in macrophages controlling the inflammatory response. Recently, we reported visfatin as a PPARγ target gene in human macrophages. In this study, we examined whether LXR regulates macrophage visfatin expression. Synthetic LXR ligands decreased visfatin gene expression in a LXR-dependent manner in human and murine macrophages. The decrease of visfatin mRNA was paralleled by a decrease of protein secretion. Consequently, a modest and transient decrease of NAD⁺ concentration was observed. Interestingly, LXR activation decreased the PPARγ-induced visfatin gene and protein secretion in human macrophages.Our results identify visfatin as a gene oppositely regulated by the LXR and PPARγ pathways in human macrophages.