Is autopsy tissue a valid control for epilepsy surgery tissue in microRNA studies?

MicroRNAs (miRNAs) are differentially expressed in the brain under pathologic conditions and may therefore represent both therapeutic targets and diagnostic or prognostic biomarkers for neurologic diseases, including epilepsy. In fact, miRNA expression profiles have been investigated in the hippocampi of patients with epilepsy in comparison with control, nonepileptic cases. Unfortunately, the interpretation of these data is difficult because surgically resected epileptic tissue is generally compared with control tissue obtained from autopsies. To challenge the validity of this approach, we performed an miRNA microarray on the laser microdissected granule cell layer of the human hippocampus obtained from surgical samples of patients with epilepsy, autoptic nonepileptic controls, and patients with autoptic epilepsy, using the latter as internal control. Unfortunately, it is extremely difficult to collect autopsy material from documented epilepsy individuals who died of non–epilepsy-related causes—we found only two such cases. However, hierarchical clustering of all samples showed that those obtained from autopsies of patients with epilepsy segregated with the other autoptic samples (controls) and not with the bioptic tissues from the surgery patients, suggesting that the origin of the tissue (surgery or autopsy) may be prevalent over the underlying pathology (epilepsy or not epilepsy). Even taking into account the limitations due to the small number of cases, this observation arises concerns on the use of autopsy tissue as control for this kind of studies

In vivo effect of pneumonia on surfactant disaturated-phosphatidylcholine kinetics in newborn infants

Bacterial pneumonia in newborns often leads to surfactant deficiency or dysfunction, as surfactant is inactivated or its production/turnover impaired. No data are available in vivo in humans on the mechanism of surfactant depletion in neonatal pneumonia. We studied the kinetics of surfactant's major component, disaturated-phosphatidylcholine (DSPC), in neonatal pneumonia, and we compared our findings with those obtained from control newborn lungs

MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy - Comparison with human epileptic samples

The identification of biomarkers of the transformation of normal to epileptic tissue would help to stratify patients at risk of epilepsy following brain injury, and inform new treatment strategies. MicroRNAs (miRNAs) are an attractive option in this direction. In this study, miRNA microarrays were performed on laser-microdissected hippocampal granule cell layer (GCL) and on plasma, at different time points in the development of pilocarpine-induced epilepsy in the rat: latency, first spontaneous seizure and chronic epileptic phase. Sixty-three miRNAs were differentially expressed in the GCL when considering all time points. Three main clusters were identified that separated the control and chronic phase groups from the latency group and from the first spontaneous seizure group. MiRNAs from rats in the chronic phase were compared to those obtained from the laser-microdissected GCL of epileptic patients, identifying several miRNAs (miR-21-5p, miR-23a-5p, miR-146a-5p and miR- 181c-5p) that were up-regulated in both human and rat epileptic tissue. Analysis of plasma samples revealed different levels between control and pilocarpine-treated animals for 27 miRNAs. Two main clusters were identified that segregated controls from all other groups. Those miRNAs that are altered in plasma before the first spontaneous seizure, like miR-9a-3p, may be proposed as putative biomarkers of epileptogenesis

Towards improved, cost-effective surveillance of Ixodes ricinus ticks and associated pathogens using species distribution modelling

Various ticks exist in the temperate hilly and pre-alpine areas of Northern Italy, where Ixodes ricinus is the more important. In this area different tick-borne pathogen monitoring projects have recently been implemented; we present here the results of a twoyear field survey of ticks and associated pathogens, conducted 2009-2010 in North-eastern Italy. The cost-effectiveness of different sampling strategies, hypothesized a posteriori based on two sub-sets of data, were compared and analysed. The same two subsets were also used to develop models of habitat suitability, using a maximum entropy algorithm based on remotely sensed data. Comparison of the two strategies (in terms of number of ticks collected, rates of pathogen detection and model accuracy) indicated that monitoring at many temporary sites was more cost-effective than monthly samplings at a few permanent sites. The two model predictions were similar and provided a greater understanding of ecological requirements of I. ricinus in the study area. Dense vegetation cover, as measured by the normalized difference vegetation index, was identified as a good predictor of tick presence, whereas high summer temperatures appeared to be a limiting factor. The study suggests that it is possible to obtain realistic results (in terms of pathogens detection and development of habitat suitability maps) with a relatively limited sampling effort and a wellplanned monitoring strategy

The Collaborative for the Research on Black Women and Girls

<p>Seven patients per group. **P<0.01 Mann-Whitney U test. Representative granule cell layer hippocampal sections from patients without granule cell pathology (B) or with type-2 GCP (C) exhibiting DAB-labeled ANTXR1-like immunoreactivity (LI). Omitting the primary antibody to estimate nonspecific signal yielded completely negative labeling (data not shown). Note a widespread increase in ANTXR1-LI in granule cells from patients with type-2 GCP (C).</p

Promoting innovation and excellence to face the rapid diffusion of Novel Psychoactive Substances (NPS) in the EU : the outcomes of the ReDNet project

Objectives: The recent emergence of new psychoactive compounds (NPS) has raised prominent challenges in the fields of drug policy, substance use research, public health and service provision. The Recreational Drugs European Network (ReDNet) project, funded by the European Commission, was implemented to improve the information stream to young people and professionals about effects/risks of NPS identifying online products and disseminating relevant information through technological tools. Methods: Regular multilingual qualitative assessments of websites, drugs fora and other online resources were carried out using the Google search engine in 8 languages from collaborating countries. These included: the UK, Norway, Belgium, Germany, Hungary, Poland, Italy and Spain. Products were tested and prevention messages were developed and disseminated via technological tools such as interactive websites, SMS alert, social networking (Facebook, Twitter), Multimedia (You Tube), Smartphone applications (iPhone), and virtual learning environments (Second Life). Results: The ReDNet project established itself as the first Europe-wide prevention programme designed for NPS based on the efficacy of novel ICT-based forms of intervention. More than 650 NPS products and combinations were identified; relevant information was disseminated to target population and advice was given to both EU/ international agencies and national policy makers. Conclusions: Web monitoring activities are essential for mapping the diffusion of NPS and the use of technological tools can be successfully incorporated in specific prevention programmes. Furthermore, the involvement of multi-disciplinary international partnerships was and continues to be fundamental for responding to such a prominent challenge.Peer reviewedSubmitted Versio

Genetic diversity and host alternation of the egg parasitoid Oencyrtus pityocampae between the pine processionary moth and caper bug

Research ArticleThe increased use of molecular tools for species identification in recent decades revealed that each of many apparently generalist parasitoids are actually a complex of morphologically similar congeners, most of which have a rather narrow host range. Ooencyrtus pityocampae (OP), an important egg parasitoid of the pine processionary moth (PPM), is considered a generalist parasitoid. OP emerges from PPM eggs after winter hibernation, mainly in spring and early summer, long before the eggs of the next PPM generation occurs. The occurrence of OP in eggs of the variegated caper bug (CB) Stenozygum coloratum in spring and summer suggests that OP populations alternate seasonally between PPM and CB. However, the identity of OP population on CB eggs seemed uncertain; unlike OP-PPM populations, the former displayed apparently high male/female ratios and lack of attraction to the PPM sex pheromone. We studied the molecular identities of the two populations since the morphological identification of the genus Ooencyrtus, and OP in particular, is difficult. Sequencing of COI and ITS2 DNA fragments and AFLP analysis of individuals from both hosts revealed no apparent differences between the OP-PPM and the OP-CB populations for both the Israeli and the Turkish OPs, which therefore supported the possibility of host alternation. Sequencing data extended our knowledge of the genetic structure of OP populations in the Mediterranean area, and revealed clear separation between East and West Mediterranean populations. The overall level of genetic diversity was rather small, with the Israeli population much less diverse than all others; possible explanations for this finding are discussed. The findings support the possibility of utilizing the CB and other hosts for enhancing biological control of the PPMinfo:eu-repo/semantics/publishedVersio

Convulsant Doses of a Dopamine D1 Receptor Agonist Result in Erk-Dependent Increases in Zif268 and Arc/Arg3.1 Expression in Mouse Dentate Gyrus

Activation of dopamine D1 receptors (D1Rs) has been shown to induce epileptiform activity. We studied the molecular changes occurring in the hippocampus in response to the administration of the D1-type receptor agonist, SKF 81297. SKF 81297 at 2.5 and 5.0 mg/kg induced behavioural seizures. Electrophysiological recordings in the dentate gyrus revealed the presence of epileptiform discharges peaking at 30–45 min post-injection and declining by 60 min. Seizures were prevented by the D1-type receptor antagonist, SCH 23390, or the cannabinoid CB1 receptor agonist, CP 55,940. The effect of SKF 81297 was accompanied by increased phosphorylation of the extracellular signal-regulated protein kinases 1 and 2 (ERK), in the granule cells of the dentate gyrus. This effect was also observed in response to administration of other D1-type receptor agonists, such as SKF83822 and SKF83959. In addition, SKF 81297 increased the phosphorylation of the ribosomal protein S6 and histone H3, two downstream targets of ERK. These effects were prevented by genetic inactivation of D1Rs, or by pharmacological inhibition of ERK. SKF 81297 was also able to enhance the levels of Zif268 and Arc/Arg3.1, two immediate early genes involved in transcriptional regulation and synaptic plasticity. These changes may be involved in forms of activity-dependent plasticity linked to the manifestation of seizures and to the ability of dopamine to affect learning and memory

Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

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