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.     

Artificial aging of Uva di Troia and Primitivo wines using oak chips inoculated with Penicillium purpurogenum

BACKGROUND: Two red wines (Primitivo and Uva di Troia) treated with oak chips inoculated with Penicillium purpurogenum were analysed in order to assess their contents of furfural, cis‐β‐methyl‐γ‐octalactone, syringol, eugenol, vanillin and 4‐vinylguaiacol. Two different sizes of oak chips (small and big, of length 2 and 8 mm respectively) and two different degrees of toasting (low and high) were used in the study. Aroma compounds were analysed by gas chromatography/mass spectrometry to determine differences among samples after 15 days of chip contact time. RESULTS: Big oak chips inoculated with P. purpurogenum increased the level of 4‐vinylguaiacol, while small oak chips inoculated with P. purpurogenum, in some conditions, increased the level of eugenol. Chip size and degree of toasting also played an important role in the content of eugenol. CONCLUSION: The use of oak chips inoculated with mould might be a promising alternative to barrel aging. Moreover, different fungal inocula could contribute to the enrichment of wine with specific compounds (e.g. 4‐vinylguaiacol and eugenol). Copyright © 2011 Society of Chemical Industry     

The influence of drying air temperature on the physical properties of dried and rehydrated eggplant

Drying processes generally cause volume and surface change of foodstuffs. Information on the porous structure and the mechanical properties of dried food products is needed for determining food quality, process design and estimating properties such as density and moisture diffusivity.In this work we investigated the structural changes induced in eggplant by convective air drying at four different temperatures (40, 50, 60 and 70 °C) and their effect on the subsequent rehydration process. Drying and rehydration kinetic curves were also measured.The changes in physical properties, such as porosity, pore-size distribution and bulk density were determined by Hg porosimetry, scanning electron microscopy and optical microscopy while their effect on the textural characteristics by dynamometric measurements.As expected, the increase of the drying air temperature causes shorter drying times. The drying temperature influences strongly the microstructure of dried samples: the porosity increases with the air temperature, but the structure is better preserved at intermediate temperature (60 °C) as confirmed by the lower firmness values with respect to the other dehydrated samples (40, 50 and 70 °C). In these latter, the longer drying time and the higher temperature, respectively, causes the development of a wrinkled structure. In particular, at 70 °C the structure of dehydrated samples appears totally broken with a consequent faster water uptake during rehydration.     

Synthesis and Characterizations of Melamine-Based Epoxy Resins

A new, easy and cost-effective synthetic procedure for the preparation of thermosetting melamine-based epoxy resins is reported. By this innovative synthetic method, different kinds of resins can be obtained just by mixing the reagents in the presence of a catalyst without solvent and with mild curing conditions. Two types of resins were synthesized using melamine and a glycidyl derivative (resins I) or by adding a silane derivative (resin II). The resins were characterized by means of chemical-physical and thermal techniques. Experimental results show that all the prepared resins have a good thermal stability, but differ for their mechanical properties: resin I exhibits remarkable stiffness with a storage modulus value up to 830 MPa at room temperature, while lower storage moduli were found for resin II, indicating that the presence of silane groups could enhance the flexibility of these materials. The resins show a pot life higher than 30 min, which makes these resins good candidates for practical applications. The functionalization with silane terminations can be exploited in the formulation of hybrid organic-inorganic composite materials.     

Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG.     

Indoor air quality in schools of a highly polluted south Mediterranean area

This study aimed at surveying lower secondary schools in southern Italy, in a highly polluted area. A community close to an industrial area and three villages in rural areas was investigated. Indoor temperature, relative humidity (RH), gaseous pollutants (CO₂ and NO₂), selected biological pollutants in indoor dust, and the indoor/outdoor mass concentration and elemental composition of PM_2.5 were ascertained. Temperature and RH were within, or close to, the comfort range, while CO₂ frequently exceeded the threshold of 1000 ppm, indicating inadequate air exchange rate. In all the classrooms, median NO₂ levels were above the WHO threshold value. Dermatophagoides p. allergen concentration was below the sensitizing threshold, while high endotoxin levels were detected in the classrooms, suggesting schools may produce significant risks of endotoxin exposure. Concentration and solubility of PM_2.5 elements were used to identify the sources of indoor particles. Indoor concentration of most elements was higher than outdoors. Resuspension was responsible for the indoor increase in soil components. For elements from industrial emission (Cd, Co, Ni, Pb, Sb, Tl, V), the indoor concentration depended on penetration from the outside. For these elements, differences in rural vs industrial concentrations were found, suggesting industrial sources may influence indoor air quality nearby schools.     

Innovative metamodelling-based process design for manufacturing: an application to Incremental Sheet Forming

The use of metamodelling techniques in process design has become indispensable to perform faster solutions reducing time to market. This approach allows the implementation of decision support tools which are easier to use than the conventional numerical simulations. In this paper, a robust metamodelling technique has been designed and its feasibility has been validated for the crucial problem of localised thinning in sheet metal forming process. The proposed methodology is based on the innovative integration between the Design of Experimental statistical method and the Kriging one. This approach, in fact, allows to analyse contemporary the continuous and categorical factors and, as a consequence, to define a single tool for changing process conditions (i.e., material and product shape). To test the reliability of the mathematical approach, the same was performed for the case study of Incremental Sheet Forming, a process strongly affected by the not homogeneous distribution of the thickness. Taking advantage of this strategy, a wide experimental investigation has been performed to build the base of knowledge of the problem both for the metamodelling design and for the validation of the decision support tool; moreover, the experimental data were utilized to set and validate a numerical model, which was subsequently used to enrich the dataset. The proposed metamodel, suitably modified according to each process peculiarities, can be generally adapted for sheet thickness prediction.