Histone Acetylation Defects in Brain Precursor Cells: A Potential Pathogenic Mechanism Causing Proliferation and Differentiation Dysfunctions in Mitochondrial Aspartate-Glutamate Carrier Isoform 1 Deficiency

Mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) deficiency is an ultra-rare genetic disease characterized by global hypomyelination and brain atrophy, caused by mutations in the SLC25A12 gene leading to a reduction in AGC1 activity. In both neuronal precursor cells and oligodendrocytes precursor cells (NPCs and OPCs), the AGC1 determines reduced proliferation with an accelerated differentiation of OPCs, both associated with gene expression dysregulation. Epigenetic regulation of gene expression through histone acetylation plays a crucial role in the proliferation/differentiation of both NPCs and OPCs and is modulated by mitochondrial metabolism. In AGC1 deficiency models, both OPCs and NPCs show an altered expression of transcription factors involved in the proliferation/differentiation of brain precursor cells (BPCs) as well as a reduction in histone acetylation with a parallel alteration in the expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, histone acetylation dysfunctions have been dissected in in vitro models of AGC1 deficiency OPCs (Oli-Neu cells) and NPCs (neurospheres), in physiological conditions and following pharmacological treatments. The inhibition of HATs by curcumin arrests the proliferation of OPCs leading to their differentiation, while the inhibition of HDACs by suberanilohydroxamic acid (SAHA) has only a limited effect on proliferation, but it significantly stimulates the differentiation of OPCs. In NPCs, both treatments determine an alteration in the commitment toward glial cells. These data contribute to clarifying the molecular and epigenetic mechanisms regulating the proliferation/differentiation of OPCs and NPCs. This will help to identify potential targets for new therapeutic approaches that are able to increase the OPCs pool and to sustain their differentiation toward oligodendrocytes and to myelination/remyelination processes in AGC1 deficiency, as well as in other white matter neuropathologies

Time dependent viscoelastic rheological response of pure, modified and synthetic bituminous binders

Bitumen is a viscoelastic material that exhibits both elastic and viscous components of response and displays both a temperature and time dependent relationship between applied stresses and resultant strains. In addition, as bitumen is responsible for the viscoelastic behaviour of all bituminous materials, it plays a dominant role in defining many of the aspects of asphalt road performance, such as strength and stiffness, permanent deformation and cracking. Although conventional bituminous materials perform satisfactorily in most highway pavement applications, there are situations that require the modification of the binder to enhance the properties of existing asphalt material. The best known form of modification is by means of polymer modification, traditionally used to improve the temperature and time susceptibility of bitumen. Tyre rubber modification is another form using recycled crumb tyre rubber to alter the properties of conventional bitumen. In addition, alternative binders (synthetic polymeric binders as well as renewable, environmental-friendly bio-binders) have entered the bitumen market over the last few years due to concerns over the continued availability of bitumen from current crudes and refinery processes. This paper provides a detailed rheological assessment, under both temperature and time regimes, of a range of conventional, modified and alternative binders in terms of the materials dynamic (oscillatory) viscoelastic response. The rheological results show the improved viscoelastic properties of polymer- and rubber-modified binders in terms of increased complex shear modulus and elastic response, particularly at high temperatures and low frequencies. The synthetic binders were found to demonstrate complex rheological behaviour relative to that seen for conventional bituminous binders

EFFECT OF PROCESSING TEMPERATURE VARIATION ON STORAGE STABILITY OF TIRE RUBBER MODIFIED BINDERS

Tire Rubber Modified Binders (TR-MBs), produced through wet process and used worldwide (e.g. asphalt rubber), have been demonstrated to provide various benefits to pavements and, moreover, represent a good opportunity for recycling tire rubber. However, this technology is still struggling to be fully adopted in Europe, mainly because of the poor stability of TR-MBs during high temperature storage, which leads to high initial costs in modifying existing asphalt plants. No-agitation TR-MBs (also known as terminal blends) are proving to be a great option and their development could also be the key to spreading the use of tire rubber in paving applications in Europe. This paper aims to enrich this field of research by presenting the results of a study focused on the compatibility of tire rubber-bitumen blends as well as on the effect of processing temperature variation on storage stability of TR-MBs. The experimental program was carried out by a preliminary selection of materials, followed by the production of the TR-MBs, via practical laboratory protocols. A continual comparison between two commercially used SBS-MBs, with high and medium levels of modification, and the TR-MBs produced, helped to understand the effect of varying the selected processing conditions on binder properties. The results showed that an accurate binder design is fundamental in order to obtain high performance binders and to improve compatibility of TR-MBs. Moreover, the study highlights that dynamic mechanical analysis (DMA) is a suitable technique to assess the storage stability of modified binders

Design Procedures for Soil-Lime Stabilization for Road and Railway Embankments. Part 2-Experimental Validation

As detailed in Part 1, the most common Italian Technical Specifications refer to different design methodologies for design of lime-soil mixtures, some being quite different from those internationally adopted. Therefore, it seemed appropriate to the Authors to compare these methodologies, via a wide experimental program.It is shown that the Italian methodology of the National Road Agency is different not only from those used in Italy, but also from the main international standards. The experimental results highlight that a revision of that methodology is needed in order to bring it into line with what is prescribed by the European standard

Analysis of the chemical and microstructural modifications effects on the hydro-mechanical behaviour of a lime-treated clay

The paper presents the results of a characterization of kinetic characteristics of pozzolanic reaction with the aim to investigate the time-dependent modification of clay properties as a consequence of mixing with lime. Results of chemical analyses are in agreement with the increase of mechanical properties and with the observed microstructure modifications up to one year of curing time. The rate of development of pozzolanic reactions seems to be almost constant while the time required for their completion is dependent on the lime content. Pozzolanic products are responsible for the time reduction of swelling strain upon saturation as well as for the increases of yielding stress, stiffness and hydraulic conductivity. However, the data analysis proves that a significant component of settlement measured during loading may be induced by the secondary compression process (creep). These results are significant for the prediction of the long-term behaviour of the stabilized soil

L'impatto a lungo termine di un programma riabilitativo sulla qualità di vita percepita nei pazienti con fratture vertebrali da fragilità

Scopo dello studio è stato quello di valutare l'impatto di un programma riabilitativo di 10 giorni sulla qualità di vita percepita nel lungo termine. E' stato condotto quindi uno studio prospettico su pazienti afferenti all'ambulatorio multidisciplinare per la diagnosi, cura e riabilitazione delle fratture vertebrali da fragilità della AOUP. I risultati ottenuti hanno mostrato che i pazienti sottoposti a un programma riabilitativo specifico per fratture vertebrali presentavano una migliore qualità di vita percepita a distanza di 6 mesi