Fe65 Is Not Involved in the Platelet-derived Growth Factor-induced Processing of Alzheimer's Amyloid Precursor Protein, Which Activates Its Caspase-directed Cleavage

Abstract The proteolytic processing of the precursor of the β-amyloid peptides (APP) is believed to be a key event in the pathogenesis of Alzheimer's disease. This processing is activated through a pathway involving the PDGF receptor, Src, and Rac1. In this paper, we demonstrate that this pathway specifically acts on APP and requires the YENPTY motif present in the APP cytosolic domain. Considering that several results indicate that the adaptor proteins interacting with this domain affect the processing of APP, we examined their possible involvement in the PDGF-induced pathway. By using an APP-Gal4 reporter system, we observed that the overexpression of Fe65 activates APP-Gal4 cleavage, whereas X11 stabilizes APP. Although mDab1 and Jip1 have no effect, Shc induces a strong activation of APP cleavage, and the contemporary exposure of cells to PDGF causes a dramatic cooperative effect. The analysis of point mutations of the APP YENPTY motif indicates that Fe65 and PDGF function through different mechanisms. In fact, Fe65 requires the integrity of APP695 Tyr682 residue, whereas PDGF effect is dependent upon the integrity of Asn684. Furthermore, the mutation of Asp664 of APP, which is the target site for the caspase-directed APP cleavage, strongly decreases the effect of Fe65. This suggests that Fe65 activates the cleavage of APP by caspases, and in fact, caspase inhibitor Z-VEVD decreases the APP cleavage induced by Fe65. On the contrary, the effects of Shc overexpression, like those of PDGF, are completely absent in the presence of compound X and require the integrity of the Asn684 residue of APP695. The involvement of Shc in the pathway regulating APP processing is confirmed by the effects of constitutively active and dominant negative mutants of Src and Rac1

Tamarix arborea var. arborea and Tamarix parviflora: Two species valued for their adaptability to stress conditions

The choice of stress resistant and highly adaptable species is a fundamental step for landscaping and ornamental purposes in arid and coastal environments such as those in the Mediterranean basin. The genus Tamarix L. includes about 90 species with a high endurance of adversity. We investigated the water relations and photosynthetic response of Tamarix arborea (Sieb. ex Ehrenb.) Bge. var. arborea and T. parviflora DC. growing in an urban environment. Both species showed no evidence of drought or salt stress in summer, and appeared to follow two strategies with T. arborea var. arborea investing in high carbon gain at the beginning of the summer, and then reducing photosynthetic activity at the end of the season, and T. parviflora showing lower but constant levels of photosynthetic activity throughout the vegetative season. For landscaping and ornamental purposes, we suggest T. arborea var. arborea when a fast-growing, high-cover species is necessary, and T. parviflora when less-invasive species are required

Organizzazione e valutazione della didattica nella Facoltà di Economia di Modena

Il lavoro esamina gli aspetti essenziali dell'organizzazione dei corsi, del carico didattico, del calendario delle lezioni, della prestazione degli studenti, del processo di apprendimento, del sistema europeo di trasferimento dei crediti, del monitoraggio e della valutazione della didattica a livello di tutta la Facoltà di Economia.NOTA: il testo è curato da G. Ricci e M. Lalla; gli altri autori indicati hanno contribuito a scrivere uno o piú paragrafi

Age at Menarche, Growth Velocity, and Adiposity Indices in Italian Girls Aged 10 to 14

Age at menarche (AAM) is an effective marker of puberty timing but its onset could be influenced by several intrinsic and extrinsic factors. This study aimed to assess the AAM in a sample of Italian adolescents and to investigate its association with anthropometric variables. Considering the rise in overweight/obesity worldwide, special attention was paid to a possible decrease in AAM as adiposity indices increase. A longitudinal study was carried out on 117 middle school girls in Northern Italy. Data concerning menarche and anthropometric traits (standing and sitting height, weight, waist circumference, and skinfold thicknesses) were directly collected. Lower limb length and indices of adiposity and growth were calculated. The median AAM was 11.66 (95% IC: 11.31-11.68). Age-adjusted ANCOVA between mature and non-mature girls showed significant differences in growth-related traits and WHtR. No preponderance of overweight/obesity among mature participants was found. AAM was not significantly associated with weight or the growth velocity of adiposity indices in a subsample of maturers. Moreover, the median AAM of our sample was similar to that found in women born about 60 years ago in the same region. In conclusion, in addition to a stabilization of AAM since the 1960s, our results suggest that there is no significant correlation between increased adiposity and early AAM

Platelet-derived Growth Factor Induces the β-γ-Secretase-mediated Cleavage of Alzheimer's Amyloid Precursor Protein through a Src-Rac-dependent Pathway

The beta-amyloid peptide (Abeta) present in the senile plaques of Alzheimer's disease derives from the cleavage of a membrane protein, named APP, driven by two enzymes, known as beta- and gamma-secretases. The mechanisms regulating this cleavage are not understood. We have developed an experimental system to identify possible extracellular signals able to trigger the cleavage of an APP-Gal4 fusion protein, which is detected by measuring the expression of the CAT gene transcribed under the control of the Gal4 transcription factor, which is released from the membrane upon the cleavage of APP-Gal4. By using this assay, we purified a protein contained in the C6 cell-conditioned medium, which activates the cleavage of APP-Gal4 and which we demonstrated to be PDGF-BB. The APP-Gal4 processing induced by PDGF is dependent on the gamma-secretase activity, being abolished by an inhibitor of this enzyme, and is the consequence of the activation of a pathway downstream of the PDGF-receptor, which includes the non-receptor tyrosine kinase Src and the small G-protein Rac1. These findings are confirmed by the observation that a constitutively active form of Src increases Abeta generation and that, in cells stably expressing APP, the generation of A is strongly decreased by the Src tyrosine kinase inhibitor PP2

Assessing the Impact of COVID-19 Prevention Measures on Adolescent Growth in Italy

COVID-19 infection has caused increased morbidity and mortality worldwide. Several strategies have been adopted around the world to prevent its spread. Italy underwent a long lockdown for face-to-face educational activities, which were replaced with online classes. This longitudinal study aimed to analyze the effects of COVID-19 prevention measures on physical growth and body image perception in a sample of Italian adolescents who experienced the pandemic-induced lockdown in 2020. In particular, we wished to ascertain how lifestyle changes had affected their growth rates and health. Special attention was paid to increases in adiposity indicators (BMI, waist circumference, waist-to-height ratio) and weight caused by reduced physical activity, and consequent possible dissatisfaction with body image. We assessed the impact of school closures by comparing the annual growth rate and body image perception changes of adolescents (n = 60; age = 11.3 & PLUSMN; 0.4 years) who experienced this isolation with those in the following years who did not experience these restrictions (n = 68; age = 11.4 & PLUSMN; 0.3 years). As a consequence of the lockdown, our results indicate a greater annual growth rate in weight and other indices of adiposity (p < 0.05). As the virus is continuing to evolve and propagate, larger population studies can verify and confirm our findings. In promoting health policy to prevent the ongoing prevalence of obesity in adolescents, an accurate assessment of whether the increase in obesity rates during the pandemic is to be considered a temporary trend is highly recommended

Typical dairy products in Africa from local animal resources

Milk is recognised as an important element of the pastoral civilisations in Africa, where it has not only an economic value, but also a social and cultural value. The objective of this review is to identify the main African dairy products, mainly focussing on typical production processes based on the use of local animal resources. To this aim, dairy products were classified into five categories, according to the type and the production method: fresh cheese, ripened cheese, fermented milk, butter and dairy by-products. These categories give rise to an extraordinary range of local products where tradition, culture, and environmental conditions and constraints play a major role in contributing to this diversification. In some countries, some attempts are being made in order to valorise the local dairy products by establishing Slow Food Presidia or including them in the Ark of Taste compiled by Slow Food. One of the main constraints that limits the commercialisation and export of African dairy products is related to the scarce hygiene in milk production and processing, and the frequent absence of starter cultures, which result in products with non-standardised characteristics, short shelf life and high spoilage susceptibility, with consequent risks for human health. Efforts should be made to support the dairy products chain in Africa, by making production processes safer and by valuing local resources, in order to expand the internal market and the export opportunities. Development cooperation projects may play an important role in this respect and should therefore be encourage