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

All Talk and No Action: A Transcranial Magnetic Stimulation Study of Motor Cortex Activation During Action Word Production

A number of researchers have proposed that the premotor and motor areas are critical for the representation of words that refer to actions, but not objects. Recent evidence against this hypothesis indicates that the left premotor cortex is more sensitive to grammatical differences than to conceptual differences between words. However, it may still be the case that other anterior motor regions are engaged in processing a word's sensorimotor features. In the present study, we used singleand paired-pulse transcranial magnetic stimulation to test the hypothesis that left primary motor cortex is activated during the retrieval of words (nouns and verbs) associated with specific actions. We found that activation in the motor cortex increased for action words compared with non-action words, but was not sensitive to the grammatical category of the word being produced. These results complement previous findings and support the notion that producing a word activates some brain regions relevant to the sensorimotor properties associated with that word regardless of its grammatical category.Psycholog

Structure–property relationships in bionanocomposites for pipe extrusion applications

In this work, bionanocomposites based on different biodegradable polymers and two types of nanofillers, namely a nanosized calcium carbonate and an organomodified nanoclay, were produced through melt extrusion, with the aim to evaluate the possible applications of these materials as a potential alternative to traditional fossil fuel-derived polyolefins, for the production of irrigation pipes. The rheological behavior of the formulated systems was thoroughly evaluated by exploiting different flow regimes, and the obtained results indicated a remarkable effect of the introduced nanofillers on the low-frequency rheological response, especially in nanoclay-based bionanocomposites. Conversely, the shear viscosity at a high shear rate was almost unaffected by the presence of both types of nanofillers, as well as the rheological response under nonisothermal elongational flow. In addition, the analysis of the mechanical properties of the formulated materials indicated that the embedded nanofillers increased the elastic modulus when compared to the unfilled counterparts, notwithstanding a slight decrease of the material ductility. Finally, the processing behavior of unfilled biopolymers and bionanocomposites was evaluated, allowing for selecting the most suitable material and thus fulfilling the processability requirements for pipe extrusion applications

Feeding broiler chickens with arginine above recommended levels: effects on growth performance, metabolism, and intestinal microbiota

BackgroundArginine is an essential amino acid for chickens and feeding diets with arginine beyond the recommended levels has been shown to influence the growth performance of broiler chickens in a positive way. Nonetheless, further research is required to understand how arginine supplementation above the widely adopted dosages affects metabolism and intestinal health of broilers. Therefore, this study was designed to assess the effects of arginine supplementation (i.e., total arginine to total lysine ratio of 1.20 instead of 1.06-1.08 recommended by the breeding company) on growth performance of broiler chickens and to explore its impacts on the hepatic and blood metabolic profiles, as well as on the intestinal microbiota. For this purpose, 630 one-day-old male Ross 308 broiler chicks were assigned to 2 treatments (7 replicates each) fed a control diet or a crystalline L-arginine-supplemented diet for 49 d.ResultsCompared to control birds, those supplemented with arginine performed significantly better exhibiting greater final body weight at D49 (3778 vs. 3937 g; P < 0.001), higher growth rate (76.15 vs. 79.46 g of body weight gained daily; P < 0.001), and lower cumulative feed conversion ratio (1.808 vs. 1.732; P < 0.05). Plasma concentrations of arginine, betaine, histidine, and creatine were greater in supplemented birds than in their control counterparts, as were those of creatine, leucine and other essential amino acids at the hepatic level. In contrast, leucine concentration was lower in the caecal content of supplemented birds. Reduced alpha diversity and relative abundance of Firmicutes and Proteobacteria (specifically Escherichia coli), as well as increased abundance of Bacteroidetes and Lactobacillus salivarius were found in the caecal content of supplemented birds.ConclusionsThe improvement in growth performance corroborates the advantages of supplementing arginine in broiler nutrition. It can be hypothesized that the performance enhancement found in this study is associated with the increased availability of arginine, betaine, histidine, and creatine in plasma and the liver, as well as to the ability of extra dietary arginine to potentially ameliorate intestinal conditions and microbiota of supplemented birds. However, the latter promising property, along with other research questions raised by this study, deserve further investigations

Changes in airway hyperresponsiveness following smoking cessation: Comparisons between Mch and AMP

SummaryBackgroundGiven the observed association between smoking, inflammation and airway hyperresponsiveness (AHR) one may predict that smoking cessation may improve AHR. However, only a few studies have investigated the effect of smoking on AHR and their results appear to be conflicting depending on the stimulus used in their bronchoprovocation protocol. The aim of the current study was to compare changes in AHR between direct (methacholine (Mch)) and indirect (adenosine 5′monophosphate (AMP)) stimuli before and at different time points after smoking cessation in smokers with allergic rhinitis (±asthma).MethodsWe have prospectively studied changes in AHR to inhaled Mch and AMP in smokers with allergic rhinitis (±asthma), before and at 6 and 12 months after smoking cessation.ResultsIt was found that 28% (16/57) of the participants had quit smoking by the end of the study. No significant change in AHR was observed in smoking cessation failures. A significant improvement in AHR to AMP but not Mch was observed 6 months after smoking cessation in quitters; a 1.2 doubling concentrations change in PC20 AMP was measured whereas only a 0.4 doubling concentrations change was observed for PC20 Mch. However, after 12 months smoking cessation the improvement in AHR became significant for both AMP and Mch, their dose–response curves being displaced to the right to a similar extent (1.4 and 1.1 doubling concentrations for AMP and Mch, respectively).ConclusionSmoking cessation can improve AHR in smokers who quit with a 6 months improvement being reported for the airways response to AMP but not Mch. AMP challenge may detect earlier changes in AHR in smokers during smoking cessation

All talk and no action: a transcranial magnetic stimulation study of motor cortex activation during action word production

A number of researchers have proposed that the premotor and motor areas are critical for the representation of words that refer to actions, but not objects. Recent evidence against this hypothesis indicates that the left premotor cortex is more sensitive to grammatical differences than to conceptual differences between words. However, it may still be the case that other anterior motor regions are engaged in processing a word's sensorimotor features. In the present study, we used single- and paired-pulse transcranial magnetic stimulation to test the hypothesis that left primary motor cortex is activated during the retrieval of words (nouns and verbs) associated with specific actions. We found that activation in the motor cortex increased for action words compared with non-action words, but was not sensitive to the grammatical category of the word being produced. These results complement previous findings and support the notion that producing a word activates some brain regions relevant to the sensorimotor properties associated with that word regardless of its grammatical category

Phytoremediation potential of Arundo donax (Giant Reed) in contaminated soil by heavy metals

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Comparative analysis of the microbiome composition of artisanal cheeses produced in the Mediterranean area

In the PRIMA project ArtiSaneFood, the microbiological parameters of several artisanal cheeses produced in the Mediterranean area have been quantified. In this pilot study, we selected four of these artisanal cheese products from Italy, Portugal, Spain, and Morocco to investigate and compare their microbiomes in terms of taxonomy composition, presence of reads of foodborne pathogens, as well as virulence and antimicrobial resistance genes. Lactococcus, Streptococcus and Lactobacillus were the most represented genera in the Portuguese and Spanish cheeses, Streptococcus in the Italian cheese, and Enterococcus, Klebsiella, Escherichia, and Citrobacter in the Moroccan products. The correlation analysis indicated a negative association between the abundance of some lactic acid bacteria (i.e., Lactococcus, Lactobacillus, Streptococcus, and Leuconostoc) and foodborne pathogenic genera, like Escherichia and Salmonella. The analysis of pathogen abundance, virulence factors, and antimicrobial resistance genes showed a strong clusterization based on the cheese type, confirming that the presence of potential human health risk determinants was higher in the artisanal products derived from unpasteurized milk that underwent spontaneous fermentation