LDOC1 expression in fibroblasts of patients with Down syndrome

Abstract Down syndrome (DS) is characterised by intellectual disability and is caused by trisomy 21. Apoptosis is a programmed cell death process and is involved in neurodegenerative diseases such as Alzheimer. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. The leucine zipper, down regulated in cancer 1 (LDOC1) appears to be involved in the apoptotic pathways. The aim of the present work was to detect the presence of intracellular synthesis of LDOC1 protein and LDOC1 mRNA in fibroblast cultures from DS subjects. The western blot shows the presence of LDOC1 protein in fibroblasts of DS subjects but no evidence of LDOC1 protein in fibroblasts of normal subjects. LDOC1 gene mRNA expression is increased in fibroblasts from DS subjects compared to fibroblasts from normal subjects. The data obtained from this study strengthen the hypothesis that the over-expression of LDOC1 gene could play a role in determining the phenotype of individuals with DS but does not exclude that this results from apoptotic mechanisms

Poly (ADP-ribose) polymerase 1 expression in fibroblasts of Down syndrome subjects

Abstract Down syndrome (DS) is the most common chromosomal disorder. It is featured by intellectual disability and is caused by trisomy 21. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. Apoptosis is a programmed cell death process under both normal physiological and pathological conditions. Poly (ADP-ribose) polymerase 1 is a mediator of programmed-necrotic cell death and appears to be also involved in the apoptosis. The aim of the present work was to detect the intracellular distribution of PARP-1 protein using immunofluorescence techniques and the expression of PARP-1 mRNA in culture of fibroblasts of DS subjects. The analysis of the intracellular distribution of PARP-1 show a signal at the nuclear level in about 75 % of the cells of DS subjects with a slight uniformly fluorescent cytoplasm. In contrast, in about 65% of the analyzed fibroblasts of the normal subjects only a slight fluorescent was found. These observations have been confirmed by PARP-1 gene mRNA expression evaluation. The data obtained from this study strengthen the hypothesis that the over-expression of PARP-1 gene could have a role in the activation of the apoptotic pathways acting in the neurodegenerative processes in DS

Using muon rings for the optical calibration of the ASTRI telescopes for the Cherenkov Telescope Array

High-energy muons constitute a very useful tool to calibrate the total optical throughput of any telescope of the Cherenkov Telescope Array (CTA). Differences in precision and efficiency can however be present due to the variety of telescope types and sizes. In this contribution we present some preliminary results on simulated muon ring images collected by the ASTRI small sized dual-mirror (SST-2M) telescope in the basic configuration installed in Italy at the Serra La Nave observing station. ASTRI SST-2M is able, using 6% of the detected muon events, to calibrate with muons the optical throughput down to a degradation of the optical efficiency of 30%. Moreover, its precision in reconstructing the muon arrival direction is about one camera pixel, and its error on the reconstructed ring radius is 6.3%. The adopted procedures will be tested and validated with real data acquired by the prototype after the commissioning phase. The nine telescopes that will form the ASTRI mini-array, proposed to be installed at the final CTA southern site during the pre-production phase, will improve these results thanks to the higher detection efficiency and the lower optical cross-talk and after-pulse of their updated silicon photomultipliers. <P /

Helicobacter pylori Up-regulates Cyclooxygenase-2 mRNA Expression and Prostaglandin E2 Synthesis in MKN 28 Gastric Mucosal Cells in Vitro

Helicobacter pylori has been suggested to play a role in the development of gastric carcinoma in humans. Also, mounting evidence indicates that cyclooxygenase-2 overexpression is associated with gastrointestinal carcinogenesis. We studied the effect of H. pylori on the expression and activity of cyclooxygenase-1 and cyclooxygenase-2 in MKN 28 gastric mucosal cells. H. pylori did not affect cyclooxygenase-1 expression, whereas cyclooxygenase-2 mRNA levels increased by 5-fold at 24 h after incubation of MKN 28 cells with broth culture filtrates or bacterial suspensions from wild-type H. pylori strain. Also, H. pylori caused a 3-fold increase in the release of prostaglandin E2, the main product of cyclooxygenase activity. This effect was specifically related to H. pylori because it was not observed with Escherichia coli and was independent of VacA, CagA, or ammonia. H. pylori isogenic mutants specifically lacking picA or picB, which are responsible for cytokine production by gastric cells, were less effective in the up-regulation of cyclooxygenase-2 mRNA expression and in the stimulation of prostaglandin E2 release compared with the parental wild-type strain. This study suggests that development of gastric carcinoma associated with H. pylori infection may depend on the activation of cyclooxygenase-2-related events

Bortezomib modulates CHIT1 and YKL40 in monocyte-derived osteoclast and in myeloma cells

Osteolytic bone disease is a common manifestation of multiple myeloma (MM) that leads to progressive skeleton destruction and is the most severe cause of morbidity in MM patients.It results from increased osteolytic activity and decrease osteoblastic function. Activation of mammalian chitinases CHIT1 and YKL40 is associated with osteoclast (OCs) differentiation and bone digestion. In the current study, we investigated the effect of two Bortezomib’s concentration (BO) (2.5 nM and 5nM) on osteoclastogenesis by analyzing regulation of chitinase expression. OCs exposition to BO was able to inhibit the expression of different OCs markers such as RANK, CTSK, TRAP and MMP9. In addition BO-treatment reduced CHIT1 enzymatic activity and both CHIT1 and YKL40 mRNA expression levels and cytoplasmatic and secreted protein. Moreover, immunofluorescence evaluation of mature OCs showed that BO was able to translocate YKL40 into the nucleus, while CHIT1 remained into the cytoplasm. Since MM cell lines such as U266, SKM-M1 and MM1 showed high levels of CHIT1 activity, we analyzed bone resorption ability of U266 using dentin disc assay resorption pits. Silencing chitinase proteins in U266 cell line with specific siRNAs, resulted in pits number reduction on dentine discs. In conclusion, we showed that BO decreases osteoclastogenesis and reduces bone resorption in OCs and U266 cell line by modulating the chitinases CHIT1 and YKL40. These results indicate that chitinases may be a therapeutic target for bone disease in MM patients

Evaluation of the emotional phenotype and serotonergic neurotransmission of fatty acid amide hydrolase-deficient mice

By enhancing brain anandamide tone, inhibitors of fatty acid amide hydrolase (FAAH) induce anxiolytic-like effects in rodents and enhance brain serotonergic transmission. Mice lacking the faah gene (FAAH(-/-)) show higher anandamide levels. However, their emotional phenotype is still debated and their brain serotonergic tone remained unexplored. In this study, we tested FAAH(-/-) mice in the social interaction and the open field tests performed under different lighting conditions (dim and bright) since variations of the experimental context were proposed to explain opposite findings. Moreover, by microdialysis performed under dim light, we analyzed their serotonergic transmission in frontal cortex (FC) and ventral hippocampus (vHIPP). In both light conditions, FAAH(-/-) mice showed reduced emotionality, compared to wt controls, as suggested by the increased rearing and reduced thigmotaxis displayed in the open field and by the longer time spent in social interaction. Basal serotonergic tone was higher in the FC of mutant mice as compared to control mice, while no difference was observed in the vHIPP. K(+)-induced depolarization produced similar increases of serotonin in both areas of both genotypes. An acute treatment with the CB1 antagonist rimonabant completely abolished the emotional phenotype of FAAH(-/-) mice and prevented the K(+)-stimulated release of serotonin in their FC and vHIPP, without producing any effect in wt mice. Our results support the role of FAAH in the regulation of emotional reactivity and suggest that anandamide-mediated hyperactivation of CB1 is responsible for the emotional phenotype of FAAH(-/-) mice and for their enhanced serotonergic tone

3-Aroyl-1,4-diarylpyrroles inhibit chronic myeloid leukemia cell growth through an interaction with tubulin

We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. Compound 10 minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. Compound 10 significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via a mitochondria-dependent pathway. ARDAP 10 augmented the cytotoxic effects of IM in human CML cells. Compound 10 represents a robust lead compound to develop tubulin inhibitors with potential as novel treatments for CML

The Italian Earthquakes and Tsunami Monitoring and Surveillance Systems

The Osservatorio Nazionale Terremoti (ONT) is the Italian seismic operational centre for monitoring earthquake, it is part of Istituto Nazionale di Geofisica e Vulcanologia (INGV) the largest Italian research institution, with focus in Earth Sciences. INGV runs the Italian National Seismic Network (network code IV) and other networks at national scale for monitoring earthquakes and tsunami. INGV is a primary node of European Integrated Data Archive (EIDA) for archiving and distributing, continuous, quality checked seismic waveforms (strong motion and weak motion recordings). ONT designed the data acquisition system to accomplish, in near-real-time, automatic earthquake detection, hypocentre and magnitude determination and evaluation of moment tensors, shake maps and other products. Database archiving of all parametric results are closely linked to the existing procedures of the INGV seismic monitoring environment and surveillance procedures. ONT organize the Italian earthquake surveillance service and the tsunami alert service (INGV is Tsunami Service Provider of the ICG/NEAM for the entire Mediterranean basin). We provide information to the Dipartimento di Protezione Civile (DPC) and to several Mediterranean countries. Earthquakes information are revised routinely by the analysts of the Italian Seismic Bulletin. The results are published on the web and are available to the scientific community and the general public.PublishedMontreal1SR TERREMOTI - Sorveglianza Sismica e Allerta Tsunam

Consumption of energy drinks among Italian University students : a cross-sectional multicenter study

Purpose The aim of the study was to evaluate the caffeinated Energy Drinks (EDs) consumption among a large sample of Italian undergraduates and its association with some of the major lifestyle risk factors. Methods Students attending twelve public Italian universities were involved between October 2021 and May 2022. Information on socio-demographic characteristics, ED consumption, and on health-related behaviors of participants was collected by the use of a web-based questionnaire. Results A total of 2165 students participated in the study and 15.2% of them reported having used caffeinated EDs in the last six months, mainly once a month (41.5%). In comparison with non-users, ED users showed a higher proportion of males (p &lt; 0.001) and a higher father’s educational level (p = 0.003), came mainly from Northern universities (p = 0.004) and life sciences degree courses (p &lt; 0.001). Besides, ED users reported higher BMI values (p = 0.003), more particular dietary regimens (p &lt; 0.001), higher levels of weekly moderate–vigorous physical activity (p &lt; 0.001) and participation in sports (p &lt; 0.001) and in team sports (p = 0.003), and higher proportion of smokers (p &lt; 0.001) and alcohol drinkers (p = 0.005). ED use was negatively related with female gender (OR 0.546; 95% CI 0.374–0.798), the Mediterranean diet (OR 0.587; 95% CI 0.362–0.951) and coming from the center of Italy (OR 0.500; 95% CI 0.275–0.909) and positively associated with tobacco smoke (OR 1.712; 95% CI 1.176–2.492) and participation in a team sport (OR 1.686; 95% CI 1.051–2.707). Conclusion These findings could encourage figures engaged in education to increase the students’ awareness on this issue in order to prevent the excessive use of EDs and associated unhealthy behaviors, especially in the most interested subgroups