Expression of Tight Junction and Drug Efflux Transporter Proteins in an in vitro Model of Human Blood–Brain Barrier

Interendothelial cell tight junctions (TJs) proteins contribute to maintain the structural and functional integrity of the blood–brain barrier (BBB) and several efflux transporters regulate transport of compounds across BBB. A unique double compartment-model of the BBB, consisting of cerebral endothelial cells isolated from cryopreserved human glial tumors, alone and in the presence of human astroglial cells derived from the same tissue preparation was established. Endothelial cell viability and transendothelial electrical resistance (TEER) were measured in this model and three representative TJ proteins – occludin (OCLN), zonula occludens-1 (ZO-1) and claudin-5 (CLN-5) – as well as several drug efflux transporters – P-glycoprotein (P-gp), multidrug resistance protein-1 and 2 (MRP-1 and MRP-2), organic anion-transporting polypeptide-1 and 3 (oatp1 and oatp3) were analyzed at both the protein and gene transcript level. Functional activity of P-gp and MRP-1 was also assessed. Endothelial cell viability as well as TEER significantly increased in the presence of glial cells. A significant increase of expression of OCLN, ZO-1, and CLN-5 proteins as well as of several drug transporter proteins except oatp3 and MRP-1, was also found in the presence of glial cells. All the gene transcripts protein analyzed were found to be significantly increased in the presence of glial cells. A suitable functional activity of P-gp and MRP-1 was also found. These results demonstrate that this brain endothelium culture system mimics a physiologically relevant situation and may therefore provide a new tool for studying the effects of biological fluids such as serum and cerebrospinal fluid from patients with neurological disorders underlying a BBB alteration in disease pathogenesis

Preeclampsia in Lean Normotensive Normotolerant Pregnant Women Can Be Predicted by Simple Insulin Sensitivity Indexes

Certain similarities between preeclampsia and insulin resistance syndrome suggest a possible link between the 2 diseases. The aim of our study was to evaluate 3 insulin sensitivity (IS) indexes (fasting homeostasis model assessment IS [IS HOMA ], quantitative insulin sensitivity check index [IS QUICKI ], and oral glucose IS [OGIS]) early and late in pregnancy in a large number of normotensive pregnant women with a normal glucose tolerance and to test the ability of these indexes to predict the risk of subsequent preeclampsia. In all, 829 pregnant women were tested with a 75-g, 2-hour oral glucose load in 2 periods of pregnancy: early (16 to 20 weeks) and late (26 to 30 weeks). In early and late pregnancy, respectively, IS HOMA was 1.23±0.05 and 1.44±0.05 ( P <0.01), IS QUICKI was 0.40±0.002 and 0.38±0.002 ( P <0.01), and OGIS was 457±2.4 mL min −1 m −2 and 445±2.2 ( P <0.001), all confirming the reduction in insulin sensitivity during pregnancy. Preeclampsia developed in 6.4% of the pregnant women and correlated positively with the 75th centile of IS HOMA ( P =0.001), with a sensitivity of 79% in the early and 83% in the late period and a specificity of 97% in both. IS QUICKI <25th centile was also related with preeclampsia ( P =0.001), with a sensitivity of 85% in the early and 88% in the late period and a specificity of 97% in both. Judging from our findings, IS HOMA and IS QUICKI are simple tests that can pinpoint impaired insulin sensitivity early in the pregnancy. Given their high sensitivity and specificity, these indexes could be useful in predicting the development of preeclampsia in early pregnancy, before the disease become clinically evident

Educational Robotics and empowerment of executive cognitive processes: from typical development to special educational needs

This paper describes a new Educational Robotic (ER) approach aimed to empower higher cognitive functions in school-setting. As robot programming requires to mentally plan a complex sequence of actions before the motor act, ER may indeed promote several crucial cognitive processes underlying learning. The steps needed and the mental acts for robot programming may involve Executive Functions (EF), that are complex higher cognitive processes, particularly crucial in the early development, because they are the base for abstraction and logical reasoning, decision-making, sequential thinking, maintaining and updating information in memory and problem-solving. Recent studies attempting to attest with a scientific approach the effect of ER on executive functioning are described. They concern both classroom with typical development or special educational needs and rehabilitation environment for children with developmental disorder. Robotica Educativa e potenziamento dei processi cognitivi esecutivi: dallo sviluppo tipico ai bisogni educativi specialiIl presente lavoro descrive come la Robotica Educativa (RE) possa essere utilizzata per potenziare alcune funzioni cognitive di controllo. Le azioni necessarie e gli atti mentali per la programmazione di un robot implicano le Funzioni Esecutive (FE), processi cognitivi di alto ordine, particolarmente importanti durante lo sviluppo cognitivo perché coinvolti nel ragionamento logico e nell’astrazione, nel decision-making, nel pensiero sequenziale, nel problem-solving e nel mantenimento/ aggiornamento delle informazioni in memoria. Nell’articolo sono sintetizzati e discussi gli studi con cui abbiamo cercato di provare con metodi scientifici l’effetto della RE sulle FE, nel gruppo classe per bambini con sviluppo tipico o con bisogni educativi speciali, e in ambito riabilitativo per bambini con disturbo del neurosviluppo

Are pre-miR-146a and PTTG1 associated with papillary thyroid cancer?

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with a steadily increasing incidence in the last few decades worldwide. The predisposition to developing this carcinoma by the heterozygous state of rs2910164 within the precursor of the miR-146a has been reported, but recently not confirmed. Interestingly, on the same chromosome, almost 50 kb separate the pre-miR-146a from the pituitary tumor-transforming gene 1 (PTTG1), a proto-oncogene involved in several tumors, including thyroid cancers. In this study, we analyzed, using a case–control design, the genetic association between PTC and the genomic region encompassing pre-miR-146a rs2910164 and PTTG1 rs1862391 and rs2910202. We enrolled 307 affected patients and 206 healthy controls. The possible presence of thyroid nodules in controls was excluded by ultrasonography. All the cases were submitted to single- nucleotide polymorphism (SNP) genotyping of pre-miR-146a and PTTG1, and risk association analyses were carried out. The genotypic and allelic frequencies of pre-miR-146a rs2910164 were not statistically different in the patients and controls, and this SNP was not in linkage disequilibrium with the investigated PTTG1 SNPs. Consistently, meta-analyses, the first including all the affected cases published to date, did not confirm the previously reported association of the heterozygous CG genotype with PTC. The PTTG1 SNPs exhibited the same allelic frequency in the patients and controls and were not associated with the disease. In conclusion, in a well-selected Italian population, neither pre-miR-146a rs2910164 nor PTTG1 rs1862391 and rs2910202 were found to be associated with the risk of developing PTC

Effects of ram pressure on the gas distribution and star formation in the Large Magellanic Cloud

We use high resolution N-body/SPH simulations to study the hydrodynamical interaction between the Large Magellanic Cloud (LMC) and the hot halo of the Milky Way. We investigate whether ram-pressure acting on the satellite's ISM can explain the peculiarities observed in the HI distribution and the location of the recent star formation activity. Due to the present nearly edge-on orientation of the disk with respect to the orbital motion, compression at the leading edge can explain the high density region observed in HI at the south-east border. In the case of a face-on disk (according to Mastropietro et al. 2008 the LMC was moving almost face-on before the last perigalactic passage), ram-pressure directed perpendicularly to the disk produces a clumpy structure characterized by voids and high density filaments that resemble those observed by the Parkes HI survey. As a consequence of the very recent edge-on motion, the H-alpha emission is mainly concentrated on the eastern side where 30 Doradus and most of the supergiant shells are located, although some H-alpha complexes form a patchy distribution on the entire disk. In this scenario only the youngest stellar complexes show a progression in age along the leading border of the disk.Comment: 18 pages, 18 figures, submitted to MNRA

Implicit learning deficit in children with Duchenne muscular dystrophy: Evidence for a cerebellar cognitive impairment?

This study aimed at comparing implicit sequence learning in individuals affected by Duchenne Muscular Dystrophy without intellectual disability and age-matched typically developing children. A modified version of the Serial Reaction Time task was administered to 32 Duchenne children and 37 controls of comparable chronological age. The Duchenne group showed a reduced rate of implicit learning even if in the absence of global intellectual disability. This finding provides further evidence of the involvement of specific aspects of cognitive function in Duchenne muscular dystrophy and on its possible neurobiological substrate