Genetic characterization of p27kip1 and stathmin in controlling cell proliferation in vivo

The CDK inhibitor p27^kip1 is a critical regulator of cell cycle progression, but the mechanisms by which p27^kip1 controls cell proliferation in vivo are still not fully elucidated. We recently demonstrated that the microtubule destabilizing protein stathmin is a relevant p27^kip1 binding partner. To get more insights into the in vivo significance of this interaction, we generated p27^kip1 and stathmin double knock-out (DKO) mice. Interestingly, thorough characterization of DKO mice demonstrated that most of the phenotypes of p27^kip1 null mice linked to the hyper-proliferative behavior, such as the increased body and organ weight, the outgrowth of the retina basal layer and the development of pituitary adenomas, were reverted by co-ablation of stathmin. In vivo analyses showed a reduced proliferation rate in DKO compared to p27^kip1 null mice, linked, at molecular level, to decreased kinase activity of CDK4/6, rather than of CDK1 and CDK2. Gene expression profiling of mouse thymuses confirmed the phenotypes observed in vivo, showing that DKO clustered with WT more than with p27 knock-out tissue. Taken together, our results demonstrate that stathmin cooperates with p27^kip1 to control the early phase of G1 to S phase transition and that this function may be of particular relevance in the context of tumor progression.     

Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK

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Levodopa-induced plasticity: a double-edged sword in Parkinson's disease?

The long-term replacement therapy with the dopamine (DA) precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) is a milestone in the treatment of Parkinson''s disease (PD). Although this drug precursor can be metabolized into the active neurotransmitter DA throughout the brain, its therapeutic benefit is due to restoring extracellular DA levels within the dorsal striatum, which lacks endogenous DA as a consequence of the neurodegenerative process induced by the disease. In the early phases of PD, L-DOPA treatment is able to restore both long-term depression (LTD) and long-term potentiation (LTP), two major forms of corticostriatal synaptic plasticity that are altered by dopaminergic denervation. However, unlike physiological DA transmission, this therapeutic approach in the advanced phase of the disease leads to abnormal peaks of DA, non-synaptically released, which are supposed to trigger behavioural sensitization, namely L-DOPA-induced dyskinesia. This condition is characterized by a loss of synaptic depotentiation, an inability to reverse previously induced LTP. In the advanced stages of PD, L-DOPA can also induce non-motor fluctuations with cognitive dysfunction and neuropsychiatric symptoms such as compulsive behaviours and impulse control disorders. Although the mechanisms underlying the role of L-DOPA in both motor and behavioural symptoms are still incompletely understood, recent data from electrophysiological and imaging studies have increased our understanding of the function of the brain areas involved and of the mechanisms implicated in both therapeutic and adverse actions of L-DOPA in PD patients.     

Comparative LCA of concrete with recycled aggregates: a circular economy mindset in Europe

Purpose

Construction and demolition waste (C&DW) is the largest waste stream in the European Union (EU) and all over the world. Proper management of C&DW and recycled materials—including the correct handling of hazardous waste—can have major benefits in terms of sustainability and the quality of life. The Waste Framework Directive 2008/98/EC aims to have 70% of C&DW recycled by 2020. However, except for a few EU countries, only about 50% of C&DW is currently being recycled. In the present research, the environmental impact of concrete with recycled aggregates and with geopolymer mixtures is analysed. The aim of the present research is to propose a comparative LCA of concrete with recycled aggregates in the context of European politics.

Methods

Life cycle assessment (LCA) methodology is applied using Simapro© software. A cradle to grave analysis is carried out. The results are analysed based on the database Ecoinvent 3.3 and Impact 2002+.

Results

Results show that the concrete with 25% recycled aggregates is the best solution from an environmental point of view. Furthermore, geopolymer mixtures could be a valid alternative to reduce the phenomenon of “global warming”; however, the production of sodium silicate and sodium hydroxide has a great environmental impact.

Conclusions

A possible future implementation of the present study is certainly to carry out an overall assessment and to determine the most cost-effective option among the different competing alternatives through the life cycle cost analysis.