Developmental Regulation of Small-Conductance Ca²⁺-Activated K⁺ Channel Expression and Function in Rat Purkinje Neurons

Calcium transients play an important role in the early and later phases of differentiation and maturation of single neurons and neuronal networks. Small-conductance calcium-activated potassium channels of the SK type modulate membrane excitability and are important determinants of the firing properties of central neurons. Increases in the intracellular calcium concentration activate SK channels, leading to a hyperpolarization of the membrane potential, which in turn reduces the calcium inflow into the cell. This feedback mechanism is ideally suited to regulate the spatiotemporal occurrence of calcium transients. However, the role of SK channels in neuronal development has not been addressed so far. We have concentrated on the ontogenesis and function of SK channels in the developing rat cerebellum, focusing particularly on Purkinje neurons. Electrophysiological recordings combined with specific pharmacological tools have revealed for the first time the presence of an afterhyperpolarizing current (I_{AHP}) in immature Purkinje cells in rat cerebellar slices. The channel subunits underlying this current were identified as SK2 and localized by in situ hybridization and subunit-specific antibodies. Their expression level was shown to be high at birth and subsequently to decline during the first 3 weeks of postnatal life, both at the mRNA and protein levels. This developmental regulation was tightly correlated with the expression of I_{AHP} and the prominent role of SK2 channels in shaping the spontaneous firing pattern in young, but not in adult, Purkinje neurons. These results provide the first evidence of the developmental regulation and function of SK channels in central neurons

Real-time thermography system for composite welding:Undamaged baseline approach

The aerospace industry's current focus on recyclable materials and low-cost processes has accelerated research and implementation of thermoplastics matrix composites (TPC). In the last decades, researchers have researched weldability of these materials as a valid alternative to conventional mechanical fastening and adhesives, for improving the strength of the joint. Automatic induction welding of carbon fiber TPCs is one of the most promising techniques due to its numerous benefits, such as elevated energy efficiency and highly localised heat. As for all the manufacturing techniques, the importance of efficiently detecting the presence of defects during TPCs welding has pushed the need for automated real-time non-destructive evaluation (NDE) systems. This paper focuses on the development of an efficient NDE technique able to detect the presence of alterations and defects in real-time during the welding process. This technique relies on Infrared (IR) active thermography inspections performed using the induction welding heat as the source and an undamaged baseline methodology to detect differences in the heat field. The procedure was experimentally analysed by means of an apparatus capable of automatic welding of samples, performing the real-time NDE during the process. Results show the efficiency of the method to localise the damaged area and characterise the defects during the welding. The undamaged baseline methodology was proven to better clarify shape and location of defects, allowing for an efficient detection of damaged samples and areas where more detailed inspections can be performed after the welding process by means of the same IR apparatus.</p

The long-lasting protective effect of HGF in cardiomyoblasts exposed to doxorubicin requires a positive feed-forward loop mediated by ERK1,2-TIMP1-STAT3

Previous studies showed that the hepatocyte growth factor (HGF)&ndash;Met receptor axis plays long-lasting cardioprotection against doxorubicin anti-cancer therapy. Here, we explored the mechanism(s) underlying the HGF protective effect. DNA damage was monitored by histone H2AX phosphorylation and apoptosis by proteolytic cleavage of caspase 3. In doxorubicin-treated H9c2 cardiomyoblasts, the long-lasting cardioprotection is mediated by activation of the Ras/Raf/Mek/Erk (extracellular signal-regulated kinase 1,2) signaling pathway and requires Stat3 (signal transducer and activator of transcription 3) activation. The HGF protection was abrogated by the Erk1,2 inhibitor, PD98059. This translated into reduced Y705 phosphorylation and impaired nuclear translocation of Stat3, showing crosstalk between Erk1,2 and Stat3 signaling. An array of 29 cytokines, known to activate Stat3, was interrogated to identify the molecule(s) linking the two pathways. The analysis showed a selective increase in expression of the tissue inhibitor of metalloproteinases-1 (Timp1). Consistently, inhibition in cardiomyoblasts of Timp1 translation by siRNAs blunted both Stat3 activation and the cardioprotective effect of HGF. Thus, Timp1 is responsible for the generation of a feed-forward loop of Stat3 activation and helps cardiomyocytes to survive during the genotoxic stress induced by anthracyclines

Tumor cell-derived Timp-1 is necessary for maintaining metastasis-promoting Met-signaling via inhibition of Adam-10.

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Fifty Hertz electromagnetic field exposure stimulates secretion of β-amyloid peptide in cultured human neuroglioma

Recent epidemiological studies raise the possibility that individuals with occupational exposure to low frequency (50-60 Hz) electromagnetic fields (LF-EMF), are at increased risk of Alzheimer's disease (AD). However, the mechanisms through which LF-EMF may affect AD pathology are unknown. We here tested the hypothesis that the exposure to LF-EMF may affect amyloidogenic processes. We examined the effect of exposure to 3.1 mT 50 Hz LF-EMF on Abeta secretion in H4 neuroglioma cells stably overexpressing human mutant amyloid precursor protein. We found that overnight exposure to LF-EMF induces a significant increase of amyloid-beta peptide (Abeta) secretion, including the isoform Abeta 1-42, without affecting cell survival. These findings show for the first time that exposure to LF-EMF stimulates Abeta secretion in vitro, thus alluding to a potential link between LF-EMF exposure and APP processing in the brain

Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population.

Background &amp; Aims: Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to be measured. Methods: The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age- and sex-specific mortality rates recorded in Italy for person-years adequate for the enrolment period. The standardized mortality ratio (SMR) determined the relative risk of death over that of the age and sex matched general population. Results: Overall, 28/181 patients followed-up for a median period of 9.6 years (range 1–25 years) died. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3–94.8) and 62.9% (95% CI, 45.9–75.9), respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a SMR = 1.00 (95% CI, 0.72–1.35), with an SMR for non-SVR patients of 3.85 (95% CI, 3.43–4.30), for untreated of 3.01 (95% CI, 2.64–3.42) and for decompensated of 6.70 (95% CI, 5.39–8.22). Conclusions: Patients with compensated HCV cirrhosis achieving SVR by IFN obtain a main benefit levelling their survival curve to that of the general population. Wider applicability of IFN-free regimens will possibly make this achievement more generalizable