IGFBP-3 inhibits Wnt signaling in metastatic melanoma cells.

In previous works, we have shown that insulin-like growth factor-binding protein-3 (IGFBP-3), a tissue and circulating protein able to bind to IGFs, decreases drastically in the blood serum of patients with diffuse metastatic melanoma. In agreement with the clinical data, recombinant IGFBP-3 was found to inhibit the motility and invasiveness of cultured metastatic melanoma cells and to prevent growth of grafted melanomas in mice. The present work was aimed at identifying the signal transduction pathways underlying the anti-tumoral effects of IGFBP-3. We show that the anti-tumoral effect of IGFBP-3 is due to inhibition of the Wnt pathway and depends upon the presence of CD44, a receptor protein known to modulate Wnt signaling. Once it has entered the cell, IGFBP-3 binds the Wnt signalosome interacting specifically with its component GSK-3β. As a consequence, the β-catenin destruction complex dissociates from the LRP6 Wnt receptor and GSK-3β is activated through dephosphorylation, becoming free to target cytoplasmic β-catenin which is degraded by the proteasomal pathway. Altogether, the results suggest that IGFBP-3 is a novel and effective inhibitor of Wnt signaling. As IGFBP-3 is a physiological protein which has no detectable toxic effects either on cultured cells or live mice, it might qualify as an interesting new therapeutic agent in melanoma, and potentially many other cancers with a hyperactive Wnt signaling

Behavioral disturbances in dementia and beyond: Time for a new conceptual frame?

Alzheimer\u2019s disease and vascular dementia are estimated to be the most common causes of dementia, although mixed dementia could represent the most prevalent form of dementia in older adults aged more than 80 years. Behavioral disturbances are common in the natural history of dementia. However, so far, there is a paucity of studies that investigated the causal association between behavioral psychological symptoms of dementia and dementia sub-types, due to the high heterogeneity of methodology, study design and type of clinical assessment. To understand the scant evidence on such a relevant clinical issue, it could be hypothesized that a new shifting paradigm could result in a better identification of the relationship between behavioral disturbances and dementia. This narrative review provides an update of evidence on the behavioral patterns associated with different dementia sub-types and offers a potential future perspective as common ground for the development of new translational studies in the field of behavioral disturbances in dementia and the appropriateness of psychoactive treatments

Duplex DNA from Sites of Helicase-Polymerase Uncoupling Links Non-B DNA Structure Formation to Replicative Stress

BACKGROUND: Replication impediments can produce helicase-polymerase uncoupling allowing lagging strand synthesis to continue for as much as 6 kb from the site of the impediment. MATERIALS AND METHODS: We developed a cloning procedure designed to recover fragments from lagging strand near the helicase halt site. RESULTS: A total of 62% of clones from a p53-deficient tumor cell line (PC3) and 33% of the clones from a primary cell line (HPS-19I) were within 5 kb of a G-quadruplex forming sequence. Analyses of a RACK7 gene sequence, that was cloned multiple times from the PC3 line, revealed multiple deletions in region about 1 kb from the cloned region that was present in a non-B conformation. Sequences from the region formed G-quadruplex and i-motif structures under physiological conditions. CONCLUSION: Defects in components of non-B structure suppression systems (e.g. p53 helicase targeting) promote replication-linked damage selectively targeted to sequences prone to G-quadruplex and i-motif formation

Two-Fiber Self-Homodyne Transmission for Short-Reach Coherent Optical Communications

We experimentally evaluate the performance of two-fiber self-homodyne short-reach transmission, showing that it enables the use of DFB laser provided that the optical path mismatch is kept below 1 m for PM-QPSK and 0.5 m for PM-16QAM

Phase Noise Impact and scalability of self-homodyne short-reach coherent transmission using DFB lasers

We investigate on a two-fiber short-reach self-homodyne coherent transmission system without optical amplification, where the same transmission laser is used to generate a modulated signal carrying useful data and a continuous wave signal, which serves as a local oscillator at the receiver side. Target of the work is to determine by experiments and theoretical models under which conditions DFB lasers can be used instead of more expensive ECL lasers. After careful characterization of lasers phase noise in terms of linewidth as a function of the mismatch between the optical paths of the signal and of the local oscillator, the performance of two laser technologies is investigated in the proposed transmission setup, showing that commercial DFB laser can be used, provided that the optical path mismatch between the two fibers is kept below 1.8 meter for 28 GBaud PM-QPSK and 0.8 meter for PM-16QAM modulation format in combination with a soft-decision forward error correction algorithm. After an experimental demonstration, we theoretically investigate the scalability laws of the proposed systems in different configuration flavours

Outdoor characterization of dye solar cells: first results

The Centre for Hybrid and Organic Solar Energy (CHOSE) at the University of Rome Tor Vergata is focusing its efforts in developing reliable and stable dye solar cells and modules. The CHOSE development program foresees that new cells and modules will be tested both indoor and outdoor in order to have an overview of the real performances of the devices. This is generally a key point for a correct evaluation of the actual performances of any photovoltaic technology. In October 2008 an outdoor measurement campaign on Dye Solar Cells has been started. Two different types of cells have been built in the laboratory, varying the characteristics of the TiO2 film, in order to evaluate their behaviour in real outdoor environment. Data collected during the two first month of outdoor cell exposure are presented in this paper. Daily trends of cell efficiency as a function of the environmental parameters and of the cell temperature have been investigated, focusing on the cell behaviour at low irradiance levels