JMC’s Interdisciplinary Smoking Cessation Program

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Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose effects of CRIP1a on CB1R plasma membrane expression. Results indicate that CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1R by a dynamin-and clathrin-dependent process, and this was attenuated by CRIP1a over-expression. CP55940-mediated cell surface CB1R loss was followed by a cycloheximide-sensitive recovery of surface receptors (30120 min), suggesting the requirement for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB(1)Rs recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did not affect a transient rimonabant (10 nM)mediated increase in cell surface CB(1)Rs, which is postulated to be as a result of rimonabant effects on \u27non-agonist-driven\u27 internalization. These studies demonstrate a novel role for CRIP1a in agonist-driven CB1R cell surface regulation postulated to occur by two mechanisms: 1) attenuating internalization that is agonist-mediated, but not that in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking of de novo synthesized receptor to the cell surface

Controlled growth of CNT in mesoporous AAO through optimized conditions for membrane preparation and CVD operation

Anodic aluminium oxide (RAAO) membranes with a mesoporous structure were prepared under strictly controlling experimental process conditions, and physically and chemically characterized by a wide range of experimental techniques. Commercial anodic aluminium oxide (CAAO) membranes were also investigated for comparison. We demonstrated that RAAO membranes have lower content of both water and phosphorus and showed better porosity shape than CAAO. The RAAO membranes were used for template growth of carbon nanotubes (CNT) inside its pores by ethylene chemical vapour deposition (CVD) in the absence of a catalyst. A composite material, containing one nanotube for each channel, having the same length as the membrane thickness and an external diameter close to the diameter of the membrane holes, was obtained. Yield, selectivity and quality of CNTs in terms of diameter, length and arrangement (i.e. number of tubes for each channel) were optimized by investigating the effect of changing the experimental conditions for the CVD process. We showed that upon thermal treatment RAAO membranes were made up of crystallized allotropic alumina phases, which govern the subsequent CNT growth, because of their catalytic activity, likely due to their Lewis acidity. The strict control of experimental conditions for membrane preparation and CNT growth allowed us to enhance the carbon structural order, which is a critical requisite for CNT application as a substitute for copper in novel nano-interconnects

Development of children enrolled in preschools in Cuiabá, Mato Grosso State, Brazil

O objetivo foi avaliar o desenvolvimento neuropsicomotor de pré-escolares na educação infantil. Estudo de corte transversal, utilizando 38 itens do teste de Denver II. Foram avaliados todos os pré-escolares com idade entre quatro e seis anos incompletos matriculados na Rede Pública Municipal de Ensino de Cuiabá, Mato Grosso, Brasil, no período de agosto 2002 a novembro 2003. Nesse período havia 960 pré-escolares matriculados em 27 creches e duas escolas públicas. Para a análise estatística foi aplicado o teste Ç2 com intervalo de 95% de confiança e ± = 5%. Para calcular os percentis da idade em que os pré-escolares passaram em cada prova foi realizada uma regressão logística. Dos 960 pré-escolares avaliados, 67% apresentaram desempenho normal, 30,2% questionável e 2,8% anormal. Em 27/38 itens avaliados, o percentual de acertos ultrapassou 90%. O desempenho alterado predominou no sexo masculino, no grupo de cinco a seis anos. O desempenho dessa população foi muito semelhante ao dos pré-escolares norte-americanos de Denver, Colorado. O melhor resultado segundo o gênero ocorreu no sexo feminino e segundo a idade no grupo de quatro anos.The aim of this study was to assess the neuropsychomotor development of children enrolled in daycare centers and preschools. This cross-sectional study used 38 items from the Denver II test to assess four and five-year-olds enrolled in the municipal school system in Cuiabá, Mato Grosso State, Brazil, from August 2002 to November 2003. There were 960 children enrolled in 27 daycare centers and two public preschools. Statistical analysis used the Ç2 test with a 95% confidence interval and ± = 5%. Logistic regression was used to calculate the percentages with which the preschoolers passed the test at each respective age. Of the 960 preschoolers tested, 67% showed normal performance, 30.2% borderline, and 2.8% abnormal. In 27 of the 38 items, the proportion of correct answers was greater than 90%. Altered performance was more common in five-year-old boys. Performance in this sample was quite similar to that of preschoolers in Denver, Colorado, USA. The best results by gender were for girls, and by age in four-year-olds

Amino Acid-based Formula in Cowʼs Milk Allergy: Long-term Effects on Body Growth and Protein Metabolism. A Randomized Trial

Objectives: The long-term effects of amino acid-based formula (AAF) in the treatment of cow's milk allergy (CMA) are largely unexplored. The present study comparatively evaluates body growth and protein metabolism in CMA children treated with AAF or with extensively hydrolyzed whey formula (eHWF), and healthy controls. Methods: A 12-month multicenter randomized control trial was conducted in outpatients with CMA (age 5-12 m) randomized in 2 groups, treated with AAF (group 1) and eHWF (group 2), and compared with healthy controls (group 3) fed with follow-on (if age 12 months). At enrolment (T0), after 3 (T3), 6 (T6), and 12 months (T12) a clinical evaluation was performed. At T0 and T3, in subjects with CMA serum levels of albumin, urea, total protein, retinol-binding protein, and insulin-like growth factor 1 were measured. Results: Twenty-one subjects in group 1 (61.9% boys, age 6.5\ub11.5 months), 19 in group 2 (57.9% boys, age 7\ub11.7 months) and 25 subjects in group 3 (48% boys, age 5.5\ub10.5 months) completed the study. At T0, the weight z score was similar in group 1 (-0.74) and 2 (-0.76), with differences compared to group 3 (-0.17, P<0.05). At T12, the weight z score value was similar between the 3 groups without significant differences. There were no significant changes in protein metabolism in children in groups 1 and 2. Conclusion: Long-term treatment with AAF is safe and allows adequate body growth in children with CMA

The choreography of the chemical defensome response to insecticide stress: insights into the Anopheles stephensi transcriptome using RNA-Seq

Animals respond to chemical stress with an array of gene families and pathways termed "chemical defensome". In arthropods, despite many defensome genes have been detected, how their activation is arranged during toxic exposure remains poorly understood. Here, we sequenced the transcriptome of Anopheles stephensi larvae exposed for six, 24 and 48 hours to the LD50 dose of the insecticide permethrin to monitor transcriptional changes of defensome genes across time. A total of 177 genes involved in insecticide defense were differentially expressed (DE) in at least one time-point, including genes encoding for Phase 0, I, II, III and antioxidant enzymes and for Heat Shock and Cuticular Proteins. Three major patterns emerged throughout time. First, most of DE genes were down-regulated at all time-points, suggesting a reallocation of energetic resources during insecticide stress. Second, single genes and clusters of genes turn off and on from six to 48 hours of treatment, showing a modulated response across time. Third, the number of up-regulated genes peaked at six hours and then decreased during exposure. Our results give a first picture of how defensome gene families respond against toxicants and provide a valuable resource for understanding how defensome genes work together during insecticide stress