70 research outputs found
Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome
Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells
In silico analysis and modeling of putative T cell epitopes for vaccine design of Toscana virus
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A novel transport mechanism for MOMP in Chlamydophila pneumoniae and its putative role in immune-therapy
Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE−/− mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane β-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events
Phleboviruses detection in Phlebotomus perniciosus from a human leishmaniasis focus in South-West Madrid region, Spain
Acqua: inquinamento e salute. Per la costruzione di un quadro geografico ed epidemiologico
Neutralization of Toscana virus is partially mediated by antibodies to the nucleocapsid protein.
Comparison of M-MLV reverse transcriptase and Tth polymerase activity in RT-PCR of samples with low virus burden.
Rapid identification of Toscana virus by nested PCR during an outbreak in the Siena area of Italy.
The sand fly-transmitted Toscana virus is recognized as an etiologic agent of an aseptic meningitis with a long convalescence. This infection has been reported overall in many tourists or in a seronegative population circulating in endemic Mediterranean areas (Italy, Portugal, Egypt, and Cyprus). We report a cluster of acute Toscana virus infections in the local population during the summer of 1995. Twenty-one clinical cases of meningitis were investigated for the presence of Toscana virus by nested PCR performed on the S segment of the virus RNA extracted from cerebrospinal fluid samples
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