1,265 research outputs found
Role of p75 Neurotrophin Receptor in the Neurotoxicity by β-amyloid Peptides and Synergistic Effect of Inflammatory Cytokines
The neurodegenerative changes in Alzheimer's disease (AD) are elicited by the accumulation of β-amyloid peptides (Aβ), which damage neurons either directly by interacting with components of the cell surface to trigger cell death signaling or indirectly by activating astrocytes and microglia to produce inflammatory mediators. It has been recently proposed that the p75 neurotrophin receptor (p75NTR) is responsible for neuronal damage by interacting with Aβ. By using neuroblastoma cell clones lacking the expression of all neurotrophin receptors or engineered to express full-length or various truncated forms of p75NTR, we could show that p75NTR is involved in the direct signaling of cell death by Aβ via the function of its death domain. This signaling leads to the activation of caspases-8 and -3, the production of reactive oxygen intermediates and the induction of an oxidative stress. We also found that the direct and indirect (inflammatory) mechanisms of neuronal damage by Aβ could act synergistically. In fact, TNF-α and IL-1β, cytokines produced by Aβ-activated microglia, could potentiate the neurotoxic action of Aβ mediated by p75NTR signaling. Together, our results indicate that neurons expressing p75NTR, mostly if expressing also proinflammatory cytokine receptors, might be preferential targets of the cytotoxic action of Aβ in AD
L'influenza dei fattori di stress e protettivi sulle pratiche didattiche: Un'indagine sui docenti in formazione
Work-Related Stress (WRS) in the teaching profession is a focal issue in the current scientific landscape. While the main causes and consequences in terms of teachers’ mental and physical health are known, contextual causes related to organization and effects on the implementation of effective teaching practices are neglected, thus tying psychological aspects to pedagogical implications. The paper shows the results of a research conducted on a sample of 139 teachers coming out of a TFA course on ICT, aimed at investigating the main factors of SLC and its implications for the activation of inclusive teaching. The results show that the major cause of stress is the relationship with colleagues who are perceived as unsupportive. In particular, the lack of recognition of the role of support teacher prevents the implementation and testing of inclusive practices, although these are part of the teacher’s skill set.Lo Stress Lavoro Correlato (SLC) nella professione docente è un tema focale nel panorama scientifico attuale. Mentre sono note le principali cause e le conseguenze sul piano della salute mentale e fisica degli insegnanti, sono maggiormente trascurate le cause di contesto legate all’organizzazione e gli effetti sulla realizzazione di pratiche didattiche efficaci, legando così gli aspetti psicologici alle implicazioni pedagogiche. Il contributo mostra i risultati di una ricerca condotta su un campione di 139 docenti uscenti da un corso TFA sulle TIC, volta ad indagare i principali fattori di SLC e le relative implicazioni per l’attivazione di una didattica inclusiva. I risultati mostrano come la maggiore causa di stress sia la relazione con i colleghi che si percepiscono non supportivi. In particolare, il mancato riconoscimento del ruolo di docente di sostegno impedisce la realizzazione e la sperimentazione delle pratiche inclusive, benché queste facciano parte del bagaglio di competenze del docente
Autophagy-mediated neuroprotection induced by octreotide in an ex vivo model of early diabetic retinopathy
Neuronal injury plays a major role in diabetic retinopathy (DR). Our hypothesis was that the balance between neuronal death and survival may depend on a similar equilibrium between apoptosis and autophagy and that a neuroprotectant may act by influencing this equilibrium. Ex vivo mouse retinal explants were treated with high glucose (HG) for 10days and the somatostatin analog octreotide (OCT) was used as a neuroprotectant. Chloroquine (CQ) was used as an autophagy inhibitor. Apoptotic and autophagic markers were evaluated using western blot and immunohistochemistry. HG-treated explants displayed a significant increase of apoptosis paralleled by a significant decrease of the autophagic flux, which was likely to be due to increased activity of the autophagy regulator mTOR (mammalian target of rapamycin). Treatment with OCT rescued HG-treated retinal explants from apoptosis and determined an increase of autophagic activity with concomitant mTOR inhibition. Blocking the autophagic flux with CQ completely abolished the anti-apoptotic effect of OCT. Immunohistochemical observations showed that OCT-induced autophagy is localized to populations of bipolar and amacrine cells and to ganglion cells. These observations revealed the antithetic role of apoptosis and autophagy, highlighting their equilibrium from which neuronal survival is likely to depend. These data suggest the crucial role covered by autophagy, which could be considered as a molecular target for DR neuroprotective treatment strategies
Serum thyroid hormone antibodies are frequent in patients with polyglandular autoimmune syndrome type 3, particularly in those who require thyroxine treatment
Polyglandular autoimmune syndrome (PAS) type 3 consists of autoimmune thyroid
disease (AITD) coexisting with ≥1 non-thyroidal autoimmune disease (NTAID) other
than Addison’s disease and hypoparathyroidism. We evaluated the prevalence and
repertoire of thyroid hormones antibodies (THAb) in PAS-3 patients. Using a radioimmunoprecipation technique, we measured THAb (T3IgM, T3IgG, T4IgM, and T4IgG) in
107 PAS-3 patients and 88 controls (patients with AITD without any NTAID). Based
on the selective coexistence of AITD with one NTAID (chronic autoimmune gastritis,
non-segmental vitiligo or celiac disease), patients were divided into group 1 (chronic
autoimmune gastritis positive, n = 64), group 2 (non-segmental vitiligo positive, n = 24),
and group 3 (celiac disease positive, n = 15). At least one of the four THAb was detected
in 45 PAS-3 patients (42.1%) and 28 controls (31.8%, P = 0.14), with similar rates
in the three PAS-3 groups. The rates of T3Ab, T4Ab, and T3 + T4Ab were similar in
groups 1 and 2, while in group 3, T3Ab was undetected (P = 0.02). In PAS-3 patients,
the rate of levothyroxine treatment was greater in THAb-positive patients compared to
THAb-negative patients (76.7 vs. 56.1%, P = 0.03, RR = 1.4, 95% CI 1.03–1.81). Not
unexpectedly, levothyroxine daily dose was significantly higher in group 1 and group 3,
namely in patients with gastrointestinal disorders, compared to group 2 (1.9 ± 0.4 and
1.8 ± 0.3 vs. 1.5 ± 0.2 μg/kg body weight, P = 0.0005 and P = 0.004). Almost half of
PAS-3 patients have THAb, whose repertoire is similar if chronic autoimmune gastritis
or celiac disease is present. A prospective study would confirm whether THAb positivity
predicts greater likelihood of requiring levothyroxine treatment
Analisi esplorativa della statuina neolitica di Vicofertile
La statuina neolitica femminile rinvenuta in una sepoltura a Vicofertile risulta prodotta localmente (analoga per composizione alle altre ceramiche dell'area parmense) e plasmata in tre parti successivamente assemblat
Awaiting reconstruction: the time of the project
The seismic event, and catastrophic ones in general, determine essential consequences on the
body of the city and the built fabric. The wait for reconstruction brings the built environment into
a temporal limbo, between the wounds and collapses of a fabric that has been compromised
and the hopes and visions of a place which will return to be alive and safe. Historical centres are a
particularly indicative context from this perspective, as they often combine elements of a material
history stratified over time with profound values and memorial elements. The post-disaster
reconstruction sees a complex regulatory framework and varied strategies depending on cultural
and political instances at the urban and territorial scale. What responses are generated following
seismic events in those spaces of time that, although they constitute temporary phases by statute,
have been historically transformed into long-lasting phenomena? Trying to answer this complex
question, it emerges how the temporal factor produces an impact on the historical city, in its
continuity as an aggregative, territorial and landscape phenomenon
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