mTOR Signaling Components in Tumor Mechanobiology

Mechanistic target of rapamycin (mTOR) is a central signaling hub that integrates networks of nutrient availability, cellular metabolism, and autophagy in eukaryotic cells. mTOR kinase, along with its upstream regulators and downstream substrates, is upregulated in most human malignancies. At the same time, mechanical forces from the tumor microenvironment and mechanotransduction promote cancer cells’ proliferation, motility, and invasion. mTOR signaling pathway has been recently found on the crossroads of mechanoresponsive-induced signaling cascades to regulate cell growth, invasion, and metastasis in cancer cells. In this review, we examine the emerging association of mTOR signaling components with certain protein tools of tumor mechanobiology. Thereby, we highlight novel mechanisms of mechanotransduction, which regulate tumor progression and invasion, as well as mechanisms related to the therapeutic efficacy of antitumor drugs.     

Glucocerebrosidase Enhancers for Selected Gaucher Disease Genotypes by Modification of α‐1‐C‐Substituted Imino‐D‐xylitols (DIXs) by Click Chemistry

A series of hybrid analogues was designed by combination of the iminoxylitol scaffold of parent 1C9‐DIX with triazolylalkyl side chains. The resulting compounds were considered potential pharmacological chaperones in Gaucher disease. The DIX analogues reported here were synthesized by CuAAC click chemistry from scaffold 1 (α‐1‐C‐propargyl‐1,5‐dideoxy‐1,5‐imino‐D ‐xylitol) and screened as imiglucerase inhibitors. A set of selected compounds were tested as β‐glucocerebrosidase (GBA1) enhancers in fibroblasts from Gaucher patients bearing different genotypes. A number of these DIX compounds were revealed as potent GBA1 enhancers in genotypes containing the G202R mutation, particularly compound DIX‐28 (α‐1‐C‐[(1‐(3‐trimethylsilyl)propyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl]‐1,5‐dideoxy‐1,5‐imino‐D ‐xylitol), bearing the 3‐trimethylsilylpropyl group as a new surrogate of a long alkyl chain, with approximately threefold activity enhancement at 10 nM . Despite their structural similarities with isofagomine and with our previously reported aminocyclitols, the present DIX compounds behaved as non‐competitive inhibitors, with the exception of the mixed‐type inhibitor DIX‐28.     

Comparison of low cost shielding-absorbing cement paste building materials in X-band frequency range using a variety of wastes

General concern for potential health effects of 24 h electromagnetic fields (EMF) exposure has increased over the last few years. This has led to the necessity of developing low cost electromagnetic interference (EMI) shielding and especially absorbing building materials. In the present study, the utilization of metallurgical slags and scrap tire wastes in cement paste for this purpose was investigated. Chemical and mineralogical analyses were performed to characterize all materials examined in this work. The results showed that cement paste specimens prepared by the addition of slags exhibited better shielding efficiency than similar ones based on tires waste, while absorption performance was increased and reached 80–85% for one admixture containing each waste respectively, all tested in the same X-band frequency range (8–12 GHz). Finally, the technological and environmental requirements for these cement based building materials were also established.     

Hybrid trust and reputation management for sensor networks

Wireless sensor networks are characterised by the distributed nature of their operation and the resource constraints on the nodes. Trust management schemes that are targeted at sensor networks need to be lightweight in terms of computational and communication requirements, yet powerful in terms of flexibility in managing trust between nodes of heterogeneous deployments. In this paper, we propose a trust management model that can uniformly support the needs of nodes with highly diverse network roles and capabilities, by exploiting the pre-deployment knowledge on the network topology and the information flows, and by allowing for flexibility in the trust establishment process. The model is hybrid, combining aspects from certificate-based and behaviour-based approaches on trust establishment on common evaluation processes and metrics. It enables controlled trust evolution based on network pre-configuration, and controlled trust revocation through the propagation of behaviour evaluation results made available by supervision networks. The proposed model and trust metrics have been validated through simulation. The results and analysis demonstrate its effectiveness in managing the trust relationships between nodes and clusters, while distributing the computational cost of trust evaluation operations.     

A typical Hallermann-Streiff syndrome in a 3 year old child

Iron plays a promoting role in lipid oxidation through several mechanisms. Therefore, hepatic iron deposits in the rat may lead to peroxidative damage and to alterations in the lipoprotein formation. In this report we observed that an iron overload in rats strongly reduced the hepatic lipoprotein secretion but did not affect oxidation resistance of native lipoproteins and erythrocyte lipids in spite of tocopherol and ascorbate deficiencies. Since oxidation resistance depends on the substrate to antioxidant vitamin molar ratio, our results show that an iron overload probably alters the lipoprotein lipid fatty acid composition in rats.