Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD.     

Tau Exon 10 Inclusion by PrPC through Downregulating GSK3β Activity

Tau protein is largely responsible for tauopathies, including Alzheimer’s disease (AD), where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternative splicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whose balance is physiologically regulated. In this sense, one of the several factors that regulate alternative splicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrP^C), which has different physiological functions in neuroprotection and neuronal differentiation. Moreover, a relationship between PrP^C and tau expression levels has been reported during AD evolution. For this reason, in this study we aimed to analyze the role of PrP^C and the implication of GSK3β in the regulation of tau exon 10 alternative splicing. We used AD human samples and mouse models of PrP^C ablation and tau overexpression. In addition, we used primary neuronal cultures to develop functional studies. Our results revealed a paralleled association between PrP^C expression and tau 4R isoforms in all models analyzed. In this sense, reduction or ablation of PrP^C levels induces an increase in tau 3R/4R balance. More relevantly, our data points to GSK3β activity downstream from PrP^C in this phenomenon. Our results indicate that PrP^C plays a role in tau exon 10 inclusion through the inhibitory capacity of GSK3β.     

Fluorinated Polyphosphazenes: A Survey

A general survey of fluorinated phosphazene polymers starting from their synthesis in 1965 to recent times is presented. Various types of fluorinated phosphazenes are described depending on the way fluorine atoms are connected to the polyphosphazene skeleton. The characterization, properties and practical utilization of these compounds in different domains are critically discussed.     

Correlation between configuration/conformation of zirconocenes on the stereoselectivity of the propylene polymerization reaction

Summary The catalytic performance (activity and polymer properties) of metallocenes with different symmetries in combination with methylaluminoxane (MAO) in the polymerization of propylene has been investigated at different temperatures, under standardized reaction conditions. The zirconocene rac-ethylene (⁵-1-indenyl) zirconium (IV) dichloride, with C₂ symmetry, produces isotatic polypropylene and isopropylidene(⁵-cyclopentadienyl (⁵-9-fluorenyl) zirconium (IV) dichloride, with C _S symmetry, syndiotactic polypropylene. The degree of the tacticity of these polymers increases with decreasing polymerization temperature. Only atactic polypropylene was formed with the unbridged zirconocenes bis(⁵-cyclopentadienyl) zirconium (IV) dichloride and bis(⁵-indenyl zirconium (IV) dichloride at any temperature investigated (10–60°C).     

Solar barometric distillation for seawater desalting part I: Basic layout and operational/technical features

The report presents an innovative solar barometric distillation technology for seawater desalting (SW-SBD) which has several attractive features such as: (1) efficient vacuum solar collectors of simple construction; (2) a barometric layout for quasi-steady operation at subatmospheric pressure; (3) a demister system of simple mechanical construction; and (4) an electronic control system regulating plant productivity parameters on available solar radiation flux. The proposed seawater desalting technology consists of single-effect distillation with water vapor produced and heated at subatmospheric pressure in a solar collector loop; the basic layout, operational features, and energy efficiency are presented and analysed in detail. Subsequent reports will provide technico-economical data from prototype desalting plants in view of industrial implementation. A promising specific electric energy consumption,∼2 kWm³ offresh water produced, was found by estimating pumping power requirements of major SW-SBD plant pumps. A sizable reduction in produced water cost with respect to an existing solar seawater desalting plant in Abu Dhabi is expected on the basis of a preliminary economic evaluation for a ∼100 m³/d plant prototype.     

Effect of ethanol administration on fatty acid desaturation

The effect of ethanol on the fatty acid desaturation by rat liver has been studied using liquid diets of different composition. Acute ethanol administration increased triacylglycerols of total liver lipids, but did not modify significantly the lipidic composition of microsomes. The Δ6 and Δ5 desaturases were inhibited by ethanol whereas the Δ9 desaturase and fatty acid synthetase were apparently modified only by diet composition. NADH-cytochrome (cyt.) c reductase was partially inhibited, whereas NADH-cyt. b₅ reductase remained practically unaltered and NADPH-cyt. c reductase activity was enhanced. Decreased electrons supplied by the microsomal cyt. b₅ electron transport chain would not be the reason for the inhibition of Δ6 and Δ5 desaturases by ethanol.     

Fiber Coating Concepts for Brittle-Matrix Composites

The current interest in tough, high-temperature materials has motivated fiber coating development for brittle-matrix composites with brittle reinforcements. Such coatings are needed for controlled interface debonding and frictional sliding. The system investigated in this study was sapphire fiber-reinforced alumina. This system is thermochemically stable for severe use conditions, exhibits little thermal expansion mismatch, and utilizes the excellent strength and creep resistance of sapphire reinforcements. Porous oxide and refractory metal coatings which satisfy requirements for toughness improvement in these composites were identified by employing a variety of newly developed mechanical testing techniques for determining the interfacial fracture energies and sliding resistances.     

Sulfate attack of concrete building foundations induced by sewage waters

A case history of a severe degradation of concrete foundation plinths and piers of an about-35-year-old building located in Northern Italy is described. Significant amounts of gypsum, near ettringite and/or thaumasite were detected by X-ray diffraction analyses performed on ground concrete samples. Large gypsum crystals were mainly located at the interface between the cement paste and aggregates, as observed by scanning electron microscopy coupled to energy-dispersive spectroscopy microanalysis. The degradation effects increased with decreasing the distance of concrete structures from an absorbing well located in the courtyard of the building. The well was recognized as the sulfate source due to the microorganism metabolism of sulfur compounds present in the sewage. Consequences of this attack were a very poor bond strength between cement paste and aggregates and a severe cracking of the concrete cover of the steel reinforcement.     

Hybrid materials based on metal oxides and poly(organophosphazenes)

In this paper the sol-gel preparation of hybrid materials made of metal oxide and polytorganophosphazenel components is described. The main problem focused on during this research was to avoid phase separation in order to get homogeneous materials. This problem was pursued looking at the formation of genuine chemical bonds between the exploited polyphosphazenes and the inorganic composite networks. Investigations on the thermal, mechanical, and electroconductive properties of the synthesized, phosphazene-containing composite materials showed that these matrices presented improved mechanical and thermal features with respect to those of the original phosphazene macromolecule, while the ionic conductivities of the prepared molecular hybrids doped with lithium or silver trillate are of the same order of magnitude as those measured for the neat, original phosphazene substrate.Presented at the Ist Italian Workshop on Cyclo- and Polytphosphazenel Materials. February 15–16, 1996. at the CNR Research Area in Padova, Italy.