Serotonin Trasporter Tracks Similarities Between Sids And Idiopathic Alte

Polymorphisms in the serotonin transporter (5HTT) (SLC6A4 encoding 5HTT) as a predisposing factor in infant death. Considering stric corrispondence between 5HTT and MAOA genotypic and allelic data inIALTE and SIDS, we hypothesize that the two syndromes are different expression of a common ethiopathogenesis

Right ventricular morpho-functional remodelling in never treated hypertensives: role of aortic pressure and bi-ventricular parameters

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AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons

Functional as well as structural alterations in mitochondria size, shape and distribution are precipitating, early events in progression of Alzheimer's Disease (AD). We reported that a 20\u201322 kDa NH2-tau fragment (aka NH2htau), mapping between 26 and 230 amino acids of the longest human tau isoform, is detected in cellular and animal AD models and is neurotoxic in hippocampal neurons. The NH2htau \u2013but not the physiological full-length protein\u2013 interacts with A\u3b2 at human AD synapses and cooperates with it in inhibiting the mitochondrial ANT-1-dependent ADP/ATP exchange. Here we show that the NH2htau also adversely affects the interplay between the mitochondria dynamics and their selective autophagic clear- ance. Fragmentation and perinuclear mislocalization of mitochondria with smaller size and density are early found in dying NH2htau-expressing neurons. The specific effect of NH2htau on quality control of mitochondria is accompanied by (i) net reduction in their mass in correlation with a general Parkin- mediated remodeling of membrane proteome; (ii) their extensive association with LC3 and LAMP1 autoph- agic markers; (iii) bioenergetic deficits and (iv) in vitro synaptic pathology. These results suggest that NH2htau can compromise the mitochondrial biology thereby contributing to AD synaptic deficits not only by ANT-1 inactivation but also, indirectly, by impairing the quality control mechanism of these organelles

AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons

Functional as well as structural alterations in mitochondria size, shape and distribution are precipitating, early events in progression of Alzheimer's Disease (AD). We reported that a 20\u201322 kDa NH2-tau fragment (aka NH2htau), mapping between 26 and 230 amino acids of the longest human tau isoform, is detected in cellular and animal AD models and is neurotoxic in hippocampal neurons. The NH2htau \u2013but not the physiological full-length protein\u2013 interacts with A\u3b2 at human AD synapses and cooperates with it in inhibiting the mitochondrial ANT-1-dependent ADP/ATP exchange. Here we show that the NH2htau also adversely affects the interplay between the mitochondria dynamics and their selective autophagic clear- ance. Fragmentation and perinuclear mislocalization of mitochondria with smaller size and density are early found in dying NH2htau-expressing neurons. The specific effect of NH2htau on quality control of mitochondria is accompanied by (i) net reduction in their mass in correlation with a general Parkin- mediated remodeling of membrane proteome; (ii) their extensive association with LC3 and LAMP1 autoph- agic markers; (iii) bioenergetic deficits and (iv) in vitro synaptic pathology. These results suggest that NH2htau can compromise the mitochondrial biology thereby contributing to AD synaptic deficits not only by ANT-1 inactivation but also, indirectly, by impairing the quality control mechanism of these organelles

Gene expression profiling of hypoxic response in different models of senescent endothelial cells

Endothelial cells senescence is a physiological process affecting vascular integrity. It can contribute to heart and arterial stiffening and remodeling, impaired angiogenesis, defective vascular repair, and with an increasing prevalence of atherosclerosis. Drugs used as antineoplastic therapies, targeting tumor as well as endothelial cells, can also trigger endothelial cells senescence. We demonstrated that a short pulse of axitinib, a specific inhibitor of vascular endothelial growth factor receptors, induces cell senescence of endothelial cells. Here, we performed a high-throughput gene expression analysis to characterize the response of proliferating versus senescent endothelial cells to hypoxia, the main trigger of neo-angiogenetic phenomena in tumors. We compared the response to hypoxia of replicative senescent cells, with that of axitinib or of DNA damage-induced senescence. Overall, we enlightened common and specific responses to different senescence inducers and changes in the Senescent Associated Secretory Phenotype

"Un minuto per la vita": Tecniche rianimatorie in lattanti a rischio di morte improvvisa. Realizzazione di un video didattico per i genitori. ["A minute for life": resuscitation techniques in infants with risk for sudden infant death syndrome. Development of an instructional video for parents]

Aim. The present study describes a project carried out in the Center for SIDS/ALTE of the Pediatric Clinic of Varese, targeted to deliver and provide parents with a movies on PBLS titled "A Minute for Life". The impact on the parent was evaluated by applying a questionnaire.Methods. The movie "A Minute for Life" was given to 308 parents (122 fathers, mean age 35.2 and 186 mothers, mean age 28.4). All parents completed a questionnaire based on 4 parameters: 1. clarity of the content presented; 2. anxiety felt while watching the movie clip 3. reassurance related to their ability to review other times the movie; 4. the perception of its usefulness.Results. Regarding the clarity of content, the results provide evidence :that 231 parents (75% of the sample) rated him "very clear", while 77 subjects (25%) considered it "quite clear". On the possibility of being able to have at home, 277 parents (90% of subjects) believed it would be very reassuring to see it back Home. According to 231 parents (75% of the sample) the vision of the movie does not convey anxiety, while 77 of them (25% of subjects) felt slightly concerned in relation to vision. With regard to the overall assessment of the movie, all parents (308, 100% of the sample) agreed about its extreme usefulness.Conclusion. Our study opens the way for further prospective studies regarding the appropriateness and usefulness of the movie. It's also important to consider the release of the movie to all new parents and the possibility of giving first aid courses open to all those who want to be able to act with promptness and expertise if and when necessary.Aim. The present study describes a project carried out in the Center for SIDS/ALTE of the Pediatric Clinic of Varese, targeted to deliver and provide parents with a movies on PBLS titled "A Minute for Life". The impact on the parent was evaluated by applying a questionnaire. Methods. The movie "A Minute for Life" was given to 308 parents (122 fathers, mean age 35.2 and 186 mothers, mean age 28.4). All parents completed a questionnaire based on 4 parameters: 1. clarity of the content presented; 2. anxiety felt while watching the movie clip 3. reassurance related to their ability to review other times the movie; 4. the perception of its usefulness. Results. Regarding the clarity of content, the results provide evidence that 231 parents (75% of the sample) rated him "very clear", while 77 subjects (25%) considered it "quite clear". On the possibility of being able to have at home, 277 parents (90% of subjects) believed it would be very reassuring to see it back Home. According to 231 parents (75% of the sample) the vision of the movie does not convey anxiety, while 77 of them (25% of subjects) felt slightly concerned in relation to vision. With regard to the overall assessment of the movie, all parents (308, 100% of the sample) agreed about its extreme usefulness. Conclusion. Our study opens the way for further prospective studies regarding the appropriateness and usefulness of the movie. It's also important to consider the release of the movie to all new parents and the possibility of giving first aid courses open to all those who want to be able to act with promptness and expertise if and when necessary

Oxygen sensing is impaired in ATM-defective cells

The transcription factor hypoxia-inducible factor 1α (HIF-1α) is a master regulator of cell adaptation to decreasing oxygen levels. High oxygen tension promotes proteosomal degradation of HIF-1α via a pathway that requires hydroxylation of prolines 402 and 564. Low oxygen tension, hypoxia, inactivates the hydroxylases responsible for these modifications through a mechanism that is not fully understood but appears to require mitochondrial respiration and production of reactive oxygen species, ROS. Cells from individuals affected by ataxia telangiectasia syndrome have an impaired mitochondrial activity and a constitutive oxidative stress. Here we show that, in these cells, HIF-1α is efficiently degraded even in condition of low oxygen tension. Mechanistically this depends from a blunted increase in intracellular concentration of ROS in response to hypoxia which in turn is due to an increased cellular capacity of buffering ROS. We suggest that regulation of HIF-1α stability may depend on fold change of ROS relative to the basal level more than on their absolute value. Since elevated oxidative stress is a hallmark of many human disorders our finding may be relevant to different pathologies