3,298 research outputs found

    Editorial: epilepsy and neurodevelopmental diseases

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    The association between epilepsy and neurodevelopmental diseases is well-recognized and has gained significant attention in the field of neuroscience in recent years. One of the main reasons for this interest is the need for a better understanding of the events that lead to the development and maturation of the CNS. This is a fundamental and necessary basis for potential breakthrough strategies that could guide novel and more effective disease-modifying therapeutic approaches to neurodevelopmental syndromes that are frequently characterized by severe and drug-resistant epilepsy. The perspective of such new therapeutic strategies is very promising. At the state-of-theart, patients afflicted by these rare neurodevelopmental disorders mostly rely on “symptomatic” approaches that mitigate seizures and other major symptoms but do not target the underlying biological causes of the disease. The study of this vast field of research is extremely complex and requires a multidisciplinary approach, from neuropathological to molecular and functional studies since even “simple” triggering events (e.g., a genetic mutation) during critical periods of brain development can lead to widespread effects on brain morphological and functional features

    Microscopic energy flows in disordered Ising spin systems

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    An efficient microcanonical dynamics has been recently introduced for Ising spin models embedded in a generic connected graph even in the presence of disorder i.e. with the spin couplings chosen from a random distribution. Such a dynamics allows a coherent definition of local temperatures also when open boundaries are coupled to thermostats, imposing an energy flow. Within this framework, here we introduce a consistent definition for local energy currents and we study their dependence on the disorder. In the linear response regime, when the global gradient between thermostats is small, we also define local conductivities following a Fourier dicretized picture. Then, we work out a linearized "mean-field approximation", where local conductivities are supposed to depend on local couplings and temperatures only. We compare the approximated currents with the exact results of the nonlinear system, showing the reliability range of the mean-field approach, which proves very good at high temperatures and not so efficient in the critical region. In the numerical studies we focus on the disordered cylinder but our results could be extended to an arbitrary, disordered spin model on a generic discrete structures.Comment: 12 pages, 6 figure

    PerR controls oxidative stress defence and aerotolerance but not motility-associated phenotypes of Campylobacter jejuni

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    The foodborne bacterial pathogen Campylobacter jejuni is an obligate microaerophile, which is exposed to atmospheric oxygen during transmission through the food chain. Survival under aerobic conditions requires the concerted control of oxidative stress systems, which in C. jejuni are intimately connected with iron metabolism via the PerR and Fur regulatory proteins. Here we have characterised the roles of C. jejuni PerR in oxidative stress- and motility phenotypes, and its regulon at the level of transcription, protein expression and promoter interactions. Insertional inactivation of perR in the C. jejuni reference strains NCTC 11168, 81-176 and 81116 did not result in any growth deficiencies, but strongly increased survival in atmospheric oxygen conditions, and allowed growth around filter discs infused with up to 30% H2O2 (8.8 M). Expression of catalase, alkyl hydroperoxide reductase, thioredoxin reductase and the Rrc desulforubrerythrin were increased in the perR mutant, and this was mediated at the transcriptional level as shown by electrophoretic mobility shift assays of the katA, ahpC and trxB promoters using purified PerR. Differential RNA-seq analysis of a fur perR mutant allowed the identification of eight previously unknown transcription start sites of genes controlled by either Fur and/or PerR. Finally, inactivation of perR in C. jejuni did not result in reduced motility, and did not reduce killing of Galleria melonella wax moth larvae. In conclusion, PerR plays an important role in controlling oxidative stress resistance and aerobic survival of C. jejuni, but this role does not extend into control of motility and associated phenotypes
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