Effect of Naloxone-3-Glucuronide and N -Methylnaloxone on the Motility of the Isolated Rat Colon After Morphine

The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone on rat colon motility after morphine stimulation was measured. The rat model consisted of the isolated, vascularly perfused colon. The antagonists (10−4 M, intraluminally) and morphine (10−4 M, intra-arterially) were administered from 20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by the luminal outflow. The antagonist concentrations in the luminal and venous outflow were measured by high-performance liquid chromatography. Naloxone-3-glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the luminal outflow to baseline within 10 and 20 min, respectively. These antagonists were then excreted in the luminal outflow and could not be found in the venous samples. Naloxone, produced by hydrolysis or demethylation, was not detectable. In conclusion, highly polar naloxone derivatives peripherally antagonize the motility-lowering effect of morphine in the perfused isolated rat colon, are stable, and are not able to cross the colon-mucosal blood barrie

30 days wild and the relationships between engagement with nature’s beauty, nature connectedness and well-being.

Recent research suggests that engagement with natural beauty (EWNB) is key to the well-being benefits of nature connectedness. The Wildlife Trust’s 30 Days Wild campaign provides a large-scale intervention for improving public engagement with nature and its beauty. The effect of 30 Days Wild participation on levels of EWNB and the relationship between EWNB, nature connectedness and happiness was evaluated during the 2017 campaign. Of the 49,000 people who signed up to the campaign, 308 people fully completed measures of EWNB, nature connection, health, happiness, and conservation behaviors at baseline, post-30 days and post-2 months. There were sustained and significant increases for scores in nature connection, health, happiness, and conservation behaviors. In addition, 30 Days Wild was the first intervention found to increase EWNB. Further, the significant increase in EWNB mediated the relationship between the increases in nature connectedness and happiness. In a supplementary study to understand the well-being benefits further (n = 153), emotional regulation was found to mediate the relationship between nature connectedness and happiness, but EWNB and emotional regulation were not related. The links between nature’s beauty, nature connectedness and well-being are discussed within an account of affect-regulation.N/

Human, Nature, Dynamism: The Effects of Content and Movement Perception on Brain Activations during the Aesthetic Judgment of Representational Paintings

Movement perception and its role in aesthetic experience have been often studied, within empirical aesthetics, in relation to the human body. No such specificity has been defined in neuroimaging studies with respect to contents lacking a human form. The aim of this work was to explore, through functional magnetic imaging (f MRI), how perceived movement is processed during the aesthetic judgment of paintings using two types of content: human subjects and scenes of nature. Participants, untutored in the arts, were shown the stimuli and asked to make aesthetic judgments. Additionally, they were instructed to observe the paintings and to rate their perceived movement in separate blocks. Observation highlighted spontaneous processes associated with aesthetic experience, whereas movement judgment outlined activations specifically related to movement processing. The ratings recorded during aesthetic judgment revealed that nature scenes received higher scored than human content paintings. The imaging data showed similar activation, relative to baseline, for all stimuli in the three tasks, including activation of occipito-temporal areas, posterior parietal, and premotor cortices. Contrast analyses within aesthetic judgment task showed that human content activated, relative to nature, precuneus, fusiform gyrus, and posterior temporal areas, whose activation was prominent for dynamic human paintings. In contrast, nature scenes activated, relative to human stimuli, occipital and posterior parietal cortex/precuneus, involved in visuospatial exploration and pragmatic coding of movement, as well as central insula. Static nature paintings further activated, relative to dynamic nature stimuli, central and posterior insula. Besides insular activation, which was specific for aesthetic judgment, we found a large overlap in the activation pattern characterizing each stimulus dimension (content and dynamism) across observation, aesthetic judgment, and movement judgment tasks. These findings support the idea that the aesthetic evaluation of artworks depicting both human subjects and nature scenes involves a motor component, and that the associated neural processes occur quite spontaneously in the viewer. Furthermore, considering the functional roles of posterior and central insula, we suggest that nature paintings may evoke aesthetic processes requiring an additional proprioceptive and sensori-motor component implemented by “motor accessibility” to the represented scenario, which is needed to judge the aesthetic value of the observed painting

Antisense properties of tricyclo-DNA

Tricyclo (tc)-DNA belongs to the class of conformationally constrained DNA analogs that show enhanced binding properties to DNA and RNA. We prepared tc-oligonucleotides up to 17 nt in length, and evaluated their binding efficiency and selectivity towards complementary RNA, their biological stability in serum, their RNase H inducing potential and their antisense activity in a cellular assay. Relative to RNA or 2′-O-Me-phosphorothioate (PS)-RNA, fully modified tc-oligodeoxynucleotides, 10-17 nt in length, show enhanced selectivity and enhanced thermal stability by ∼1°C/modification in binding to RNA targets. Tricyclodeoxyoligonucleotides are completely stable in heat-deactivated fetal calf serum at 37°C. Moreover, tc-DNA-RNA duplexes are not substrates for RNase H. To test for antisense effects in vivo, we used HeLa cell lines stably expressing the human β-globin gene with two different point mutations in the second intron. These mutations lead to the inclusion of an aberrant exon in β-globin mRNA. Lipofectamine-mediated delivery of a 17mer tc-oligodeoxynucleotide complementary to the 3′-cryptic splice site results in correction of aberrant splicing already at nanomolar concentrations with up to 100-fold enhanced efficiency relative to a 2′-O-Me-PS-RNA oligonucleotide of the same length and sequence. In contrast to 2′-O-Me-PS-RNA, tc-DNA shows antisense activity even in the absence of lipofectamine, albeit only at much higher oligonucleotide concentration

Antisense properties of tricyclo-DNA

Tricyclo (tc)-DNA belongs to the class of conformationally constrained DNA analogs that show enhanced binding properties to DNA and RNA. We prepared tc-oligonucleotides up to 17 nt in length, and evaluated their binding efficiency and selectivity towards complementary RNA, their biological stability in serum, their RNase H inducing potential and their antisense activity in a cellular assay. Relative to RNA or 2′-O-Me-phosphorothioate (PS)-RNA, fully modified tc-oligodeoxynucleotides, 10–17 nt in length, show enhanced selectivity and enhanced thermal stability by ∼1°C/modification in binding to RNA targets. Tricyclodeoxyoligonucleotides are completely stable in heat-deactivated fetal calf serum at 37°C. Moreover, tc-DNA–RNA duplexes are not substrates for RNase H. To test for antisense effects in vivo, we used HeLa cell lines stably expressing the human β-globin gene with two different point mutations in the second intron. These mutations lead to the inclusion of an aberrant exon in β-globin mRNA. Lipofectamine-mediated delivery of a 17mer tc-oligodeoxynucleotide complementary to the 3′-cryptic splice site results in correction of aberrant splicing already at nanomolar concentrations with up to 100-fold enhanced efficiency relative to a 2′-O-Me-PS-RNA oligonucleotide of the same length and sequence. In contrast to 2′-O-Me-PS-RNA, tc-DNA shows antisense activity even in the absence of lipofectamine, albeit only at much higher oligonucleotide concentrations

Effect of naloxone-3-glucuronide and N-methylnaloxone on the motility of the isolated rat colon after morphine

The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone on rat colon motility after morphine stimulation was measured. The rat model consisted of the isolated, vascularly perfused colon. The antagonists (10(-4) M, intraluminally) and morphine (10(-4) M, intra-arterially) were administered from 20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by the luminal outflow. The antagonist concentrations in the luminal and venous outflow were measured by high-performance liquid chromatography. Naloxone-3-glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the luminal outflow to baseline within 10 and 20 min, respectively. These antagonists were then excreted in the luminal outflow and could not be found in the venous samples. Naloxone, produced by hydrolysis or demethylation, was not detectable. In conclusion, highly polar naloxone derivatives peripherally antagonize the motility-lowering effect of morphine in the perfused isolated rat colon, are stable, and are not able to cross the colon-mucosal blood barrier

The "Mast Cell and Basophil Club" of the French Society for Immunology

International audienceMast cells and basophils are best known for their key role during allergic responses [1]. Yet, they also have pivotal functions in innate and acquired (via IgE) defense mechanisms against microbes and parasites as well as in the neutralization of certain toxins such as snake venoms, through the release of proteases and other mediators contained in their cytoplasmic granules [2, 3] (Figure 1, example of a mast cell releasing cytoplasmic granules stained using fluorochrome‐labeled avidin, red). Recent work indicates that these cells have also important functions in a much broader range of inflammatory and pathological conditions including autoimmune diseases, cardiovascular diseases, skin diseases, neuroinflammatory disease and even cancer. However, the mechanisms by which mast cells and basophils mediate their functions in these settings remain largely unknown. Not surprisingly, these new aspects of mast cell and basophil biology have raised interest in the immunology community, with the emergence of new groups focused on studying their involvement in the maintenance of homeostasis and the promotion of disease