Tau Cleavage Contributes to Cognitive Dysfunction in Strepto-Zotocin-Induced Sporadic Alzheimer’s Disease (sAD) Mouse Model

Tau cleavage plays a crucial role in the onset and progression of Alzheimer’s Disease (AD), a widespread neurodegenerative disease whose incidence is expected to increase in the next years. While genetic and familial forms of AD (fAD) occurring early in life represent less than 1%, the sporadic and late-onset ones (sAD) are the most common, with ageing being an important risk factor. Intracerebroventricular (ICV) infusion of streptozotocin (STZ)—a compound used in the systemic induction of diabetes due to its ability to damage the pancreatic β cells and to induce insulin resistance—mimics in rodents several behavioral, molecular and histopathological hallmarks of sAD, including memory/learning disturbance, amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress and brain glucose hypometabolism. We have demonstrated that pathological truncation of tau at its N-terminal domain occurs into hippocampi from two well-established transgenic lines of fAD animal models, such as Tg2576 and 3xTg mice, and that it’s in vivo neutralization via intravenous (i.v.) administration of the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) is strongly neuroprotective. Here, we report the therapeutic efficacy of 12A12mAb in STZ-infused mice after 14 days (short-term immunization, STIR) and 21 days (long-term immunization regimen, LTIR) of i.v. delivery. A virtually complete recovery was detected after three weeks of 12A12mAb immunization in both novel object recognition test (NORT) and object place recognition task (OPRT). Consistently, three weeks of this immunization regimen relieved in hippocampi from ICV-STZ mice the AD-like up-regulation of amyloid precursor protein (APP), the tau hyperphosphorylation and neuroinflammation, likely due to modulation of the PI3K/AKT/GSK3-β axis and the AMP-activated protein kinase (AMPK) activities. Cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations occurring in STZ-infused mice were also strongly attenuated by 12A12mAb delivery. These results further strengthen the causal role of N-terminal tau cleavage in AD pathogenesis and indicate that its specific neutralization by non-invasive administration of 12A12mAb can be a therapeutic option for both fAD and sAD patients, as well as for those showing type 2 diabetes as a comorbidity.     

Polymer blends by self-propagating frontal polymerization

The use of self-propagating frontal polymerization to produce polymer blends has been investigated. A homogeneous solution of monomer, polymer (of a second monomer), and initiator is initially heated at a specific location to start a polymerization front that propagates along the system. The obtained polymerization reaction is very fast compared with diffusion, so that the two types of macromolecules remain homogeneously distributed, as in the original monomer/polymer solution. In the case of two incompatible polymers, the system has no time to reach the equilibrium condition where phase separation occurs and a polymer blend is obtained in the form of a metastable solution. Applications to two incompatible pairs (methyl methacrylate-styrene and methyl methacrylate-methacrylic acid) are discussed. Moreover, it has been found that the presence of inert polymer in the initial mixture improves the process performance, leading to more stable propagation fronts, lower front temperatures, and higher monomer conversions. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 70: 2695–2702, 1998     

Formal specification of beliefs in multi-agent systems

The goal of this paper is to present a logical framework for the formalization of agents' mutual beliefs in a Multi Agent system. The approach is based on a combination of extensional specifications of beliefs and context-based (finite) presentation of the specifications by employing a particular class of Multi Context systems. The extensional specification provides a set-theoretic characterization of beliefs in terms of sets closed under certain conditions. Its finite presentation is provided by using as constructors inference rules inside a Multi Context system. The resulting framework allows for capturing many relevant cases of real (not omniscient) agents, which are very common in Multi Agent scenarios embedded in real world environments. In order to substantiate this claim, two Multi Agent scenarios are formally specified in detail in the specification framework. ©1999 John Wiley & Sons, Inc.     

Characterization of Low‐Molecular‐Weight PLA using HPLC

HPLC is applied and assessed as an effective tool to investigate both the production of PLA by polycondensation and its corresponding degradation. A new HPLC calibration procedure, through which it is possible to fully characterize LMW PLA samples by determining the concentration of each individual oligomer, is developed. A comparison between HPLC, ¹H NMR spectroscopy and non‐aqueous solution titration is also reported in order to confirm the reliability of the proposed method. Finally, the proposed analytical technique is applied to monitor the development of a polycondensation reaction performed at 150 °C and 133.3 mbar for 12 h.

     

Scratch Resistance Enhancement of Polymer Coatings

This review presents the state of the art regarding the improvement of scratch resistance of polymeric coatings. In particular, our attention is focused on the effect of inorganic nanometric fillers on the scratch resistance of organic coatings. Two main strategies are described for the achievement of such nanostructured hybrid organic/inorganic coatings: either a top‐down or a bottom‐up approach.

     

Magnetic resonance butterfly coils: Design and application for hyperpolarized C studies

Hyperpolarized ¹³C magnetic resonance spectroscopy in pig models enables cardiac metabolism assessment and provides a powerful tool for heart physiology studies, although the low molar concentration of derivate metabolites gives rise to technological limitations in terms of data quality. The design of dedicated coils capable of providing large field of view with high Signal-to-Noise Ratio (SNR) data is of fundamental importance.